Interactions between integrin αIIbβ3 and the serotonin transporter regulate serotonin transport and platelet aggregation in mice and humans
Open accessAbstract
The essential contribution of the antidepressant-sensitive serotonin (5-HT) transporter SERT (which is encoded by the SLC6A4 gene) to platelet 5-HT stores suggests an important role of this transporter in platelet function. Here, using SERT-deficient mice, we have established a role for constitutive SERT expression in efficient ADP- and thrombin-triggered platelet aggregation. Additionally, using pharmacological blockers of SERT and the vesicular monoamine transporter (VMAT), we have identified a role for ongoing 5-HT release and SERT activity in efficient human platelet aggregation. We have also demonstrated that fibrinogen, an activator of integrin alphaIIbbeta3, enhances SERT activity in human platelets and that integrin alphaIIbbeta3 interacts directly with the C terminus of SERT. Consistent with these findings, knockout mice lacking integrin beta3 displayed diminished platelet SERT activity. Conversely, HEK293 cells engineered to express human SERT and an activated form of integrin beta3 exhibited enhanced SERT function that coincided with elevated SERT surface expression. Our results support an unsuspected role of alphaIIbbeta3/SERT associations as well as alphaIIbbeta3 activation in control of SERT activity in vivo that may have broad implications for hyperserotonemia, cardiovascular disorders, and autism.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Linkage studies in ASD have implicated the 17q11.2 region containing Slc6a4.
“linkage studies in ASD have implicated the 17q11.2 region containing Slc6a4 [50, 51].”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [51]
Cites
Bengel, D., Murphy, D. L., Andrews, A. M., Wichems, C. H., Feltner, D. E., Heils, A., Mößner, R., Westphal, H., & Lesch, K. (1998) · Molecular Pharmacology · doi:10.1124/mol.53.4.649 · Cited by 719 · see citing works
Platelet Hyperreactivity and Prognosis in Survivors of Myocardial Infarction
Trip, M. D., Cats, V. M., van Capelle, F. J. L., & Vreeken, J. (1990) · New England Journal of Medicine · doi:10.1056/nejm199005313222201 · Cited by 614 · see citing works
Gershon, M. D. (2004) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2004.02180.x · Cited by 521 · see citing works
Integrin signaling to the actin cytoskeleton
DeMali, K. A., Wennerberg, K., & Burridge, K. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00109-1 · Cited by 504 · see citing works
Walther, D. J., Peter, J.-U., Winter, S., Höltje, M., Paulmann, N., Grohmann, M., Vowinckel, J., Alamo-Bethencourt, V., Wilhelm, C. S., Ahnert-Hilger, G., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)01014-6 · Cited by 475 · see citing works
Ramamoorthy, S., & Blakely, R. (1999) · Science · doi:10.1126/science.285.5428.763 · Cited by 392 · see citing works
Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse
Chavis, P., & Westbrook, G. L. (2001) · Nature · doi:10.1038/35077101 · Cited by 332 · see citing works
Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene
Eddahibi, S., Hanoun, N., Lanfumey, L., Lesch, K., Raffestin, B., Hamon, M., & Adnot, S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8678 · Cited by 318 · see citing works
Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype
Ozaki, N., Goldman, D. A., Kaye, W. H., Plotnicov, K. H., Greenberg, B. D., Lappalainen, J., Rudnick, G., & Murphy, D. L. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001365 · Cited by 275 · see citing works
Qian, Y., Melikian, H. E., Rye, D., Levey, A. I., & Blakely, R. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-02-01261.1995 · Cited by 254 · see citing works
Sauer, W. H., Berlin, J. A., & Kimmel, S. E. (2003) · Circulation · doi:10.1161/01.cir.0000079172.43229.cd · Cited by 247 · see citing works
Bauman, A. L., Apparsundaram, S., Ramamoorthy, S., Wadzinski, B. E., Vaughan, R. A., & Blakely, R. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-20-07571.2000 · Cited by 235 · see citing works
Zhu, C.-B., Carneiro, A. M., Dostmann, W. R., Hewlett, W. A., & Blakely, R. D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410858200 · Cited by 228 · see citing works
Self-citationSamuvel, D. J., Jayanthi, L. D., Bhat, N. R., & Ramamoorthy, S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3754-04.2005 · Cited by 215 · see citing works
Platelet Reactivity in Depressed Patients Treated With Paroxetine
Musselman, D. L., Marzec, U. M., Manatunga, A. K., Penna, S., Reemsnyder, A., Knight, B. T., Барон, А. В., Hanson, S. R., & Nemeroff, C. B. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.9.875 · Cited by 205 · see citing works
The influence of selective serotonin reuptake inhibitors on human platelet serotonin
Pittendreigh, C., Solomons, K., & Maurer‐Spurej, E. (2003) · Thrombosis and Haemostasis · doi:10.1160/th03-05-0330 · Cited by 200 · see citing works
Regulated phosphorylation and trafficking of antidepressant-sensitive serotonin transporter proteins
Blakely, R., Ramamoorthy, S., Schroeter, S., Qian, Y., Apparsundaram, S., Galli, A., & DeFelice, L. J. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00124-3 · Cited by 193 · see citing works
Zhu, C.-B., Hewlett, W. A., Feoktistov, I., Biaggioni, I., & Blakely, R. (2004) · Molecular Pharmacology · doi:10.1124/mol.65.6.1462 · Cited by 168 · see citing works
Protein phosphatase 2A-mediated cross-talk between p38 MAPK and ERK in apoptosis of cardiac myocytes
Liu, Q., & Hofmann, P. A. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01050.2003 · Cited by 159 · see citing works
Coutinho, A. M., Sousa, I., Martins, M., Correia, C., Morgadinho, T., Bento, C., Marques, C., Ataíde, A., Miguel, T. S., Moore, J. H., et al. (2007) · Human Genetics · doi:10.1007/s00439-006-0301-3 · Cited by 153 · see citing works
Hanna, G. L. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00097-3 · Cited by 150 · see citing works
β3 Tyrosine Phosphorylation in αIIbβ3 (Platelet Membrane GP IIb-IIIa) Outside-in Integrin Signaling
Nannizzi‐Alaimo, L., Prasad, K. S. S., & Phillips, D. R. (2001) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1616222 · Cited by 135 · see citing works
The PlA2 polymorphism of integrin β3 enhances outside-in signaling and adhesive functions
Vijayan, K. V., Goldschmidt‐Clermont, P. J., Roos, C. M., & Bray, P. F. (2000) · Journal of Clinical Investigation · doi:10.1172/jci6982 · Cited by 135 · see citing works
Nakatani, D., Sato, H., Sakata, Y., Shiotani, I., Kinjo, K., Mizuno, H., Shimizu, M., Ito, H., Koretsune, Y., Hirayama, A., et al. (2005) · American Heart Journal · doi:10.1016/j.ahj.2005.03.062 · Cited by 131 · see citing works
Jayanthi, L. D., Samuvel, D. J., Blakely, R. D., & Ramamoorthy, S. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.009555 · Cited by 123 · see citing works
Depression and cardiovascular comorbidity
Glassman, A. H. (2007) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2007.9.1/ahglassman · Cited by 123 · see citing works
Gawaz, M., Loftus, J. C., Bajt, M. L., Frojmovic, M. M., Plow, E. F., & Ginsberg, M. H. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115412 · Cited by 121 · see citing works
Stored human platelets retain full aggregation potential in response to pairs of aggregating agents
DiMinno, G., Silver, M., & Murphy, S. (1982) · Blood · doi:10.1182/blood.v59.3.563.563 · Cited by 118 · see citing works
Guilluy, C., Rolli‐Derkinderen, M., Tharaux, P., Melino, G., Pacaud, P., & Loirand, G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604195200 · Cited by 117 · see citing works
Carneiro, A. M. D., & Blakely, R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603877200 · Cited by 107 · see citing works
Ramamoorthy, S., Samuvel, D. J., Buck, E. R., Rudnick, G., & Jayanthi, L. D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611353200 · Cited by 100 · see citing works
Variation in ITGB3 is associated with whole-blood serotonin level and autism susceptibility
Weiss, L. A., Kosova, G., Delahanty, R., Jiang, L., Cook, E. H., Ober, C., & Sutcliffe, J. S. (2006) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201644 · Cited by 92 · see citing works
Briones, N. J., Malcolm, K. C., Nick, J. A., & Worthen, G. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204455200 · Cited by 89 · see citing works
Pharmacologic Treatment of Depression in Patients With Heart Disease
Roose, S. P., & Miyazaki, M. (2005) · Psychosomatic Medicine · doi:10.1097/01.psy.0000163455.43226.bf · Cited by 76 · see citing works
Serebruany, V. L., Glassman, A. H., Malinin, A., Atar, D., Sane, D. C., Oshrine, B. R., Ferguson, J. J., & O’Connor, C. M. (2003) · European Journal of Heart Failure · doi:10.1016/s1388-9842(03)00005-9 · Cited by 74 · see citing works
de Virgilio, M., Kiosses, W. B., & Shattil, S. J. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200402064 · Cited by 70 · see citing works
An assessment of platelet aggregation induced by 5-hydroxytryptamine
Hilton, B. P., & Cumings, J. N. (1971) · Journal of Clinical Pathology · doi:10.1136/jcp.24.3.250 · Cited by 69 · see citing works
Genome-wide association study identifies ITGB3 as a QTL for whole blood serotonin
Weiss, L. A., Veenstra-VanderWeele, J. M., Newman, D. L., Kim, S., Dytch, H. E., McPeek, M. S., Cheng, S., Ober, C., Cook, E. H., & Abney, M. (2004) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201239 · Cited by 68 · see citing works
Nishihira, K., Yamashita, A., Tanaka, N., Kawamoto, R., Imamura, T., Yamamoto, R., Eto, T., & Asada, Y. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01702.x · Cited by 67 · see citing works
Bioenergetics of serotonin transport by membrane vesicles derived from platelet dense granules.
Fishkes, H., & Rudnick, G. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)83830-9 · Cited by 64 · see citing works
PlA polymorphism of glycoprotein IIIa and risk of adverse events after coronary stent placement
Kastrati, A., Koch, W., Gawaz, M., Mehilli, J., Böttiger, C., Schömig, K., von Beckerath, N., & Schömig, A. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00709-9 · Cited by 64 · see citing works
Nair, G. V., Gurbel, P. A., O’Connor, C. M., Gattis, W. A., Murugesan, S. R., & Serebruany, V. L. (1999) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)00284-2 · Cited by 63 · see citing works
Glycoprotein IIIa PlA1/A2 polymorphism and sudden cardiac death
Mikkelsson, J., Perola, M., Laippala, P., Penttilä, A., & Karhunen, P. J. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00871-8 · Cited by 60 · see citing works
Protein Phosphatase 1 Associates with the Integrin αIIb Subunit and Regulates Signaling
Vijayan, K. V., Liu, Y., Li, T.-T., & Bray, P. F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400239200 · Cited by 52 · see citing works
Genetics of Arterial Prothrombotic Risk States
Williams, M. S., & Bray, P. F. (2001) · Experimental Biology and Medicine · doi:10.1177/153537020122600504 · Cited by 46 · see citing works
Ansah, T.-A., Ramamoorthy, S., Montañez, S., Daws, L. C., & Blakely, R. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.047134 · Cited by 41 · see citing works
Vijayan, K. V., Liu, Y., Sun, W., Ito, M., & Bray, P. F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500872200 · Cited by 41 · see citing works
The GPIIIa (β3 integrin) PlA polymorphism in the early development of coronary atherosclerosis
Mikkelsson, J., Perola, M., Penttilä, A., Goldschmidt‐Clermont, P. J., & Karhunen, P. J. (2001) · Atherosclerosis · doi:10.1016/s0021-9150(00)00683-3 · Cited by 39 · see citing works
Vijayan, K. V., & Bray, P. F. (2006) · Experimental Biology and Medicine · doi:10.1177/153537020623100504 · Cited by 30 · see citing works
5‐Hydroxytryptamine as a potent migration enhancer of human aortic endothelial cells
Matsusaka, S., & Wakabayashi, I. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.10.068 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The expanded biology of serotonin
Berger, M., Gray, J. A., & Roth, B. L. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.60.042307.110802 · Cited by 2,100 · see citing works
SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation
Kristensen, A. S., Andersen, J., Jørgensen, T. N., Sørensen, L., Eriksen, J., Loland, C. J., Strømgaard, K., & Gether, U. (2011) · Pharmacological Reviews · doi:10.1124/pr.108.000869 · Cited by 865 · see citing works
The serotonin system in autism spectrum disorder: From biomarker to animal models
Muller, C. L., Anacker, A. M. J., & Veenstra-VanderWeele, J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.11.010 · Cited by 531 · see citing works
Veenstra-VanderWeele, J., Muller, C. L., Iwamoto, H., Sauer, J. E., Owens, W. A., Shah, C. R., Cohen, J., Mannangatti, P., Jessen, T., Thompson, B. J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112345109 · Cited by 333 · see citing works
Self-citationSerotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions
Scotton, W. J., Hill, L. J., Williams, A. C., & Barnes, N. M. (2019) · International Journal of Tryptophan Research · doi:10.1177/1178646919873925 · Cited by 267 · see citing works
Molecular Mechanisms of SERT in Platelets: Regulation of Plasma Serotonin Levels
Mercado, C. P., & Kilic, F. (2010) · Molecular Interventions · doi:10.1124/mi.10.4.6 · Cited by 262 · see citing works
Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19
Sukhatme, V. P., Reiersen, A. M., Vayttaden, S. J., & Sukhatme, V. V. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.652688 · Cited by 187 · see citing works
Wang, F., Knutson, K. R., Alcaino, C., Linden, D. R., Gibbons, S. J., Kashyap, P., Grover, M., Oeckler, R. A., Gottlieb, P. A., Li, H. J., et al. (2016) · The Journal of Physiology · doi:10.1113/jp272718 · Cited by 188 · see citing works
Vesicular and Plasma Membrane Transporters for Neurotransmitters
Blakely, R. D., & Edwards, R. H. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005595 · Cited by 169 · see citing works
Developing zebrafish models of autism spectrum disorder (ASD)
Stewart, A., Nguyen, M., Wong, K., Poudel, M. K., & Kalueff, A. V. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.11.014 · Cited by 151 · see citing works
Regulation of monoamine transporters: Role of transporter phosphorylation
Ramamoorthy, S., Shippenberg, T. S., & Jayanthi, L. D. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.09.009 · Cited by 151 · see citing works
Veenstra-VanderWeele, J., & Blakely, R. D. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.185 · Cited by 128 · see citing works
Going with the Flow: Trafficking‐Dependent and ‐Independent Regulation of Serotonin Transport
Steiner, J. A., Carneiro, A. M. D., & Blakely, R. (2008) · Traffic · doi:10.1111/j.1600-0854.2008.00757.x · Cited by 127 · see citing works
Enhanced activity of human serotonin transporter variants associated with autism
Prasad, H. C., Steiner, J. A., Sutcliffe, J. S., & Blakely, R. (2008) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2008.0143 · Cited by 126 · see citing works
Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders
Israelyan, N., & Margolis, K. G. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.020 · Cited by 122 · see citing works
Ontogeny and regulation of the serotonin transporter: Providing insights into human disorders
Daws, L. C., & Gould, G. G. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.03.013 · Cited by 116 · see citing works
Carter, M. D., Shah, C. R., Muller, C. L., Crawley, J. N., Carneiro, A. M. D., & Veenstra-VanderWeele, J. M. (2011) · Autism Research · doi:10.1002/aur.180 · Cited by 112 · see citing works
Platelets: emerging facilitators of cellular crosstalk in rheumatoid arthritis
Olumuyiwa-Akeredolu, O.-O. O., Pagé, M., Soma, P., & Pretorius, E. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0187-9 · Cited by 105 · see citing works
Bismuth-Evenzal, Y., Gonopolski, Y., Gurwitz, D., Iancu, I., Weizman, A., & Rehavi, M. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.08.013 · Cited by 101 · see citing works
Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders
Gandhi, T., & Lee, C. C. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.592710 · Cited by 94 · see citing works
Liang, C., Lee, Y. H., Thein, T.-L., Fang, J., Pang, J., Ooi, E. E., Leo, Y., Ong, C. N., & Tannenbaum, S. R. (2016) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0004607 · Cited by 92 · see citing works
Reprint of: Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders
Israelyan, N., & Margolis, K. G. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2018.12.023 · Cited by 87 · see citing works
Bipolar disorder in adults with Asperger׳s Syndrome: A systematic review
Vannucchi, G., Masi, G., Toni, C., Dell’Osso, L., Erfurth, A., & Perugi, G. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.06.042 · Cited by 89 · see citing works
Garbarino, V. R., Gilman, T. L., Daws, L. C., & Gould, G. G. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.07.010 · Cited by 83 · see citing works
Platelet δ-Storage Pool Disease: An Update
Dupuis, A., Bordet, J., Eckly, A. E., & Gachet, C. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9082508 · Cited by 84 · see citing works
Chang, J. C., Tomlinson, I. D., Warnement, M. R., Ustione, A., Carneiro, A. M. D., Piston, D. W., Blakely, R., & Rosenthal, S. J. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0048-12.2012 · Cited by 78 · see citing works
Human platelets and their capacity of binding viruses: meaning and challenges?
Chabert, A., Hamzeh‐Cognasse, H., Pozzetto, B., Cognasse, F., Schattner, M. A., Gomez, R. M., & Garraud, O. (2015) · BMC Immunology · doi:10.1186/s12865-015-0092-1 · Cited by 78 · see citing works
Platelet function alterations in dengue are associated with plasma leakage
Alisjahbana, B., de Groot, P. G., Indrati, A. R., Fijnheer, R., Puspita, M., Dewi, I. M. W., van de Wijer, L., de Boer, E. M. S., Roest, M., van der Ven, A. J. A. M., et al. (2014) · Thrombosis and Haemostasis · doi:10.1160/th14-01-0056 · Cited by 74 · see citing works
Ziu, E., Mercado, C. P., Li, Y., Singh, P., Ahmed, B. A., Freyaldenhoven, S. T., Lensing, S., Ware, J. L., & Kilic, F. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2012.02.004 · Cited by 73 · see citing works
Serotonergic mechanisms enhance platelet-mediated thrombogenicity
López-Vílchez, I., Díaz‐Ricart, M., Navalón, F., Gómez‐Gil, E., Gastó, C., Escolar, G., & Galan, A. M. (2009) · Thrombosis and Haemostasis · doi:10.1160/th08-12-0810 · Cited by 72 · see citing works
Liu, Y., Wei, L., Laskin, D. L., & Fanburg, B. L. (2010) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2010-0078oc · Cited by 71 · see citing works
iTRAQ‐Based Proteomic Analysis Reveals Protein Profile in Plasma from Children with Autism
Shen, L., Zhang, K., Feng, C., Chen, Y., Li, S., Iqbal, J., Liao, L., Zhao, Y., & Zhai, J. (2017) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201700085 · Cited by 69 · see citing works
The Role of Serotonin beyond the Central Nervous System during Embryogenesis
Lv, J., & Liu, F. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00074 · Cited by 70 · see citing works
Serotonin as a Mitogen in the Gastrointestinal Tract: Revisiting a Familiar Molecule in a New Role
Shah, P. A., Park, C. J., Shaughnessy, M. P., & Cowles, R. A. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.05.008 · Cited by 67 · see citing works
Oved, K., Morag, A., Pasmanik-Chor, M., Rehavi, M., Shomron, N., & Gurwitz, D. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.86 · Cited by 66 · see citing works
Autocrine and paracrine regulatory functions of platelet serotonin
Mammadova‐Bach, E., Mauler, M., Braun, A., & Duerschmied, D. (2018) · Platelets · doi:10.1080/09537104.2018.1478072 · Cited by 66 · see citing works
Tseng, Y., Chiang, M.-L., Huang, T., Su, K., Lane, H., & Lai, Y.-C. (2010) · Thrombosis Research · doi:10.1016/j.thromres.2010.09.017 · Cited by 65 · see citing works
The Role of Serotonin beyond the Central Nervous System during Embryogenesis
Lv, J., & Liu, F. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fnpit.2017.00400 · Cited by 65 · see citing works
Lorsung, E., Ramanujam, K., & Cao, R. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.642745 · Cited by 63 · see citing works
Novel aspects of enteric serotonergic signaling in health and brain-gut disease
Colle, A. D., Israelyan, N., & Margolis, K. G. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00173.2019 · Cited by 65 · see citing works
Mostafa, G. A., & AL-Ayadhi, L. Y. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-71 · Cited by 60 · see citing works
Integrin adhesion in brain assembly: From molecular structure to neuropsychiatric disorders
Jaudon, F., Thalhammer, A., & Cingolani, L. A. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14859 · Cited by 57 · see citing works
Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes
Napolioni, V., Lombardi, F., Sacco, R., Curatolo, P., Manzi, B., Alessandrelli, R., Militerni, R., Bravaccio, C., Lenti, C., Saccani, M., et al. (2010) · European Journal of Human Genetics · doi:10.1038/ejhg.2010.180 · Cited by 59 · see citing works
Moya, P. R., Wendland, J. R., Rubenstein, L. M., Timpano, K. R., Heiman, G. A., Tischfield, J. A., King, R. A., Andrews, A. M., Ramamoorthy, S., McMahon, F. J., et al. (2013) · Movement Disorders · doi:10.1002/mds.25460 · Cited by 57 · see citing works
Rose’Meyer, R. B. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-37 · Cited by 56 · see citing works
Hyperserotonemia in autism: activity of 5HT-associated platelet proteins
Hranilović, D., Bujas-Petković, Z., Tomičić, M., Bordukalo-Nikšić, T., Blažević, S. A., & Čičin‐Šain, L. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0192-2 · Cited by 54 · see citing works
Multifaceted Regulations of the Serotonin Transporter: Impact on Antidepressant Response
Baudry, A., Pietri, M., Launay, J., Kellermann, O., & Schneider, B. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00091 · Cited by 55 · see citing works
Steiner, J. A., Carneiro, A. M., Wright, J., Matthies, H. J. G., Prasad, H. C., Nicki, C. K., Dostmann, W. R., Buchanan, C. C., Corbin, J. D., Francis, S. H., et al. (2009) · Molecular Brain · doi:10.1186/1756-6606-2-26 · Cited by 48 · see citing works
Duerschmied, D., Canault, M., Lievens, D., Brill, A. G., Cifuni, S. M., Bäder, M., & Wagner, D. D. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03476.x · Cited by 48 · see citing works
Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders
Mitra, I., Lavillaureix, A., Yeh, E., Traglia, M., Tsang, K. M., Bearden, C. E., Rauen, K. A., & Weiss, L. A. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006516 · Cited by 46 · see citing works
Blood platelet research in autism spectrum disorders: In search of biomarkers
Padmakumar, M., Raes, E. V., Geet, C. V., & Freson, K. (2019) · Research and Practice in Thrombosis and Haemostasis · doi:10.1002/rth2.12239 · Cited by 47 · see citing works
Matondo, A. B., Punt, C. A., Homberg, J. R., Toussaint, M. J. M., Kisjes, R., Korporaal, S. J. A., Akkerman, J. W. N., Cuppen, E. P. J. G., & de Bruin, A. (2009) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.90709.2008 · Cited by 46 · see citing works
Dystrophic Serotonin Axons in Postmortem Brains from Young Autism Patients
Azmitia, E. C., Singh, J. S., Hou, X. P., & Węgiel, J. (2011) · The Anatomical Record · doi:10.1002/ar.21243 · Cited by 46 · see citing works
Hallbäck, I., Hägg, S., Eriksson, A. C., & Whiss, P. A. (2012) · Pharmacological Reports · doi:10.1016/s1734-1140(12)70894-0 · Cited by 45 · see citing works
Cell Adhesion Molecules and Their Involvement in Autism Spectrum Disorder
Ye, H., Liu, J., & Wu, J. Y. (2010) · Neurosignals · doi:10.1159/000322543 · Cited by 43 · see citing works
Veenstra-VanderWeele, J. M., Jessen, T. N., Thompson, B. J., Carter, M. D., Prasad, H. C., Steiner, J. A., Sutcliffe, J. S., & Blakely, R. (2009) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-009-9020-0 · Cited by 42 · see citing works
Abdel-Malik, N., Ruhé, H. G., Barwari, K., van den Dool, E. J., Meijers, J. C. M., Middeldorp, S., Buller, H. R., Schene, A. H., & Kamphuisen, P. W. (2008) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2008.03196.x · Cited by 40 · see citing works
Serotonin transporter and integrin beta 3 genes interact to modulate serotonin uptake in mouse brain
Whyte, A. J., Jessen, T. N., Varney, S., & Carneiro, A. M. D. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.09.014 · Cited by 40 · see citing works
Chronic Intake of the Selective Serotonin Reuptake Inhibitor Fluoxetine Enhances Atherosclerosis
Rami, M., Guillamat‐Prats, R., Rinne, P., Salvermoser, M., Ring, L., Bianchini, M., Blanchet, X., Megens, R. T. A., Döring, Y., Walzog, B., et al. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.310536 · Cited by 37 · see citing works
Origin of the blood hyperserotonemia of autism
Janušonis, S. (2008) · Theoretical Biology and Medical Modelling · doi:10.1186/1742-4682-5-10 · Cited by 38 · see citing works
Tseng, Y., Chiang, M.-L., Lane, H., Su, K., & Lai, Y.-C. (2013) · Thrombosis Research · doi:10.1016/j.thromres.2013.02.007 · Cited by 37 · see citing works
SSRI use and clinical outcomes in epithelial ovarian cancer
Christensen, D., Armaiz-Peña, G., Ramírez, E., Matsuo, K., Zimmerman, B., Zand, B., Shinn, E., Goodheart, M., Bender, D., Thaker, P., et al. (2016) · OncoTarget · doi:10.18632/oncotarget.8891 · Cited by 32 · see citing works
Baganz, N. L., Lindler, K. M., Zhu, C.-B., Smith, J., Robson, M. J., Iwamoto, H., Deneris, E. S., Hewlett, W. A., & Blakely, R. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.168 · Cited by 36 · see citing works
Monassier, L., Laplante, M., Ayadi, T., Doly, S., & Maroteaux, L. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.08.004 · Cited by 36 · see citing works
Genetic background modulates phenotypes of serotonin transporter Ala56 knock-in mice
Kerr, T. M., Muller, C. L., Miah, M. R., Jetter, C. S., Pfeiffer, R., Shah, C. R., Baganz, N. L., Anderson, G. M., Crawley, J. N., Sutcliffe, J. S., et al. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-35 · Cited by 36 · see citing works
Neuronal cell adhesion genes and antidepressant response in three independent samples
Fabbri, C., Crisafulli, C., Gurwitz, D., Stingl, J., Calati, R., Albani, D., Forloni, G., Calabrò, M., Martines, R., Kasper, S. F., et al. (2015) · The Pharmacogenomics Journal · doi:10.1038/tpj.2015.15 · Cited by 36 · see citing works
Becker, R. C., Dentali, F., Kuhn, C. M., Helms, M. J., Ortel, T. L., Williams, R. B., & Berger, J. S. (2012) · Thrombosis and Haemostasis · doi:10.1160/th12-03-0202 · Cited by 36 · see citing works
Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders
Mitroshina, E., Marasanova, E., & Vedunova, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216416 · Cited by 34 · see citing works
The role of serotonin in haemostasis
Bode, C., & Duerschmied, D. (2009) · Hämostaseologie · doi:10.1055/s-0037-1617140 · Cited by 35 · see citing works
HTR1B and HTR2C in autism spectrum disorders in Brazilian families
Orabona, G. M., Griesi‐Oliveira, K., Vadasz, E., Bulcão, V. L. S., Takahashi, V. N. V. O., Moreira, E. S., Furia-Silva, M., Ros-Melo, A. M. S., Dourado, F., Matioli, S. R., et al. (2008) · Brain Research · doi:10.1016/j.brainres.2008.11.007 · Cited by 34 · see citing works
Brief Report: Platelet-Poor Plasma Serotonin in Autism
Anderson, G. M., Hertzig, M. E., & McBride, P. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-011-1371-1 · Cited by 32 · see citing works
The role of Rab38 in platelet dense granule defects
Ninkovic, I., White, J. G., Rangel-Filho, A., & Datta, Y. H. (2008) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2008.03178.x · Cited by 32 · see citing works
Mazalouskas, M. D., Jessen, T. N., Varney, S., Sutcliffe, J. S., Veenstra-VanderWeele, J. M., Cook, E. H., & Carneiro, A. M. D. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.51 · Cited by 32 · see citing works
Singh, A. S., Chandra, R., Guhathakurta, S., Sinha, S., Chatterjee, A., Ahmed, S., Ghosh, S., & Rajamma, U. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.04.015 · Cited by 32 · see citing works
Acquired platelet function disorders
Brennan, Y., Levade, M., & Wård, C. (2019) · Thrombosis Research · doi:10.1016/j.thromres.2019.06.009 · Cited by 32 · see citing works
The role of β3 integrin gene variants in Autism Spectrum Disorders — Diagnosis and symptomatology
Schuch, J. B., Müller, D., Endres, R. G., Bosa, C. A., Longo, D., Schüler‐Faccini, L., Ranzan, J., Becker, M. M., Riesgo, R. D. S., & Roman, T. (2014) · Gene · doi:10.1016/j.gene.2014.09.058 · Cited by 31 · see citing works
The role of integrins in brain health and neurodegenerative diseases
Cui, Y., Rõlova, T., & Fagerholm, S. C. (2024) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2024.151441 · Cited by 30 · see citing works
Zhu, C.-B., Lindler, K. M., Campbell, N. G., Sutcliffe, J. S., Hewlett, W. A., & Blakely, R. (2011) · Molecular Pharmacology · doi:10.1124/mol.111.071399 · Cited by 30 · see citing works
Ren, W., Watts, S. W., & Fanburg, B. L. (2010) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00237.2010 · Cited by 30 · see citing works
Hoirisch-Clapauch, S., Nardi, A. E., Gris, J., & Brenner, B. (2014) · Thrombosis Research · doi:10.1016/j.thromres.2014.02.028 · Cited by 30 · see citing works
The Gain-of-Function Integrin β3 Pro33 Variant Alters the Serotonin System in the Mouse Brain
Dohn, M. R., Kooker, C. G., Bastarache, L. A., Jessen, T. N., Rinaldi, C., Varney, S., Mazalouskas, M. D., Pan, H., Oliver, K. H., Edwards, D. R. V., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1482-17.2017 · Cited by 29 · see citing works
Nurden, A. T. (2017) · Blood Reviews · doi:10.1016/j.blre.2017.03.005 · Cited by 29 · see citing works
Oliver, K. H., Duvernay, M. T., Hamm, H. E., & Carneiro, A. M. D. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.736983 · Cited by 28 · see citing works
Wolf, K., Braun, A., Haining, E. J., Tseng, Y., Kraft, P., Schuhmann, M. K., Gotru, S. K., Chen, W., Hermanns, H. M., Stoll, G., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147664 · Cited by 27 · see citing works
Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport
Roweth, H. G., Yan, R., Bedwani, N. H., Chauhan, A., Fowler, N., Watson, A. H., Malcor, J.-D. M., Sage, S. O., & Jarvis, G. E. (2018) · Scientific Reports · doi:10.1038/s41598-018-21348-3 · Cited by 26 · see citing works
Quinlan, M. A., Robson, M. J., Ye, R., Rose, K. L., Schey, K. L., & Blakely, R. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00089 · Cited by 26 · see citing works
Pagan, C., Benabou, M., Leblond, C. S., Cliquet, F., Mathieu, A., Lemière, N., Goubran‐Botros, H., Delorme, R., Leboyer, M., Callebert, J., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-020-01125-5 · Cited by 26 · see citing works
Campbell, N. G., Zhu, C.-B., Lindler, K. M., Yaspan, B. L., Kistner‐Griffin, E., Hewlett, W. A., Tate, C. G., Blakely, R., & Sutcliffe, J. S. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-28 · Cited by 26 · see citing works
Kyzar, E., Pham, M., Roth, A., Jonathan Cachat, P., Green, J., Gaikwad, S., & Kalueff, A. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2012.08.004 · Cited by 26 · see citing works
Seimandi, M., Seyer, P., Park, C. S., Vandermoere, F., Chanrion, B., Bockaert, J., Mansuy, I. M., & Marin, P. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0076-13.2013 · Cited by 25 · see citing works
Martins‐de‐Souza, D., Maccarrone, G., Ising, M., Kloiber, S. M., Lucae, S., Holsboer, F., & Turck, C. W. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.01.022 · Cited by 25 · see citing works
Is there sexual dimorphism of hyperserotonemia in autism spectrum disorder?
Shuffrey, L. C., Guter, S. J., Delaney, S., Jacob, S., Anderson, G. M., Sutcliffe, J. S., Cook, E. H., & Veenstra-VanderWeele, J. M. (2017) · Autism Research · doi:10.1002/aur.1791 · Cited by 25 · see citing works
Platelet Serotonin Transporter Function Predicts Default-Mode Network Activity
Scharinger, C., Rabl, U., Kasess, C. H., Meyer, B. M., Hofmaier, T., Diers, K., Bartova, L., Pail, G., Huf, W., Uzelac, Ž., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092543 · Cited by 24 · see citing works
Yu, W., Yen, Y.-C., Lee, Y., Tan, S., Xiao, Y., Lokman, H., Ting, A. K. T., Ganegala, H. E. W., Kwon, T., Ho, W., et al. (2019) · Molecular Brain · doi:10.1186/s13041-019-0452-5 · Cited by 24 · see citing works
Differential regulation of serotonin transporter cell surface expression
Lau, T., & Schloss, P. D. (2012) · Wiley Interdisciplinary Reviews Membrane Transport and Signalling · doi:10.1002/wmts.10 · Cited by 23 · see citing works
The C-Terminal Region of Serotonin Transporter Is Important for Its Trafficking and Glycosylation
Nobukuni, M., Mochizuki, H., Okada, S., Kameyama, N., Tanaka, A., Yamamoto, H., Amano, T., Seki, T., & Sakai, N. (2009) · Journal of Pharmacological Sciences · doi:10.1254/jphs.09195fp · Cited by 23 · see citing works
Afarideh, M., Behdadnia, A., Noshad, S., Mirmiranpour, H., Mousavizadeh, M., Khajeh, E., Rad, M. V., Mazaheri, T., Nakhjavani, M., & Esteghamati, A. (2015) · Endocrine Practice · doi:10.4158/ep14442.or · Cited by 23 · see citing works
Probst-Schendzielorz, K., Scholl, C., Efimkina, O., Ersfeld, E., Viviani, R., Serretti, A., Fabbri, C., Gurwitz, D., Lucae, S., Ising, M., et al. (2015) · Pharmacogenomics · doi:10.2217/pgs.15.31 · Cited by 22 · see citing works
MicroRNA-Mediated Regulation of ITGB3 and CHL1 Is Implicated in SSRI Action
Oved, K., Farberov, L., Gilam, A., Israel‐Elgali, I., Haguel, D., Gurwitz, D., & Shomron, N. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00355 · Cited by 22 · see citing works
Two novel, putative mechanisms of action for citalopram-induced platelet inhibition
Roweth, H. G., Cook, A. A., Moroi, M., Bonna, A., Jung, S. M., Bergmeier, W., Sage, S. O., & Jarvis, G. E. (2018) · Scientific Reports · doi:10.1038/s41598-018-34389-5 · Cited by 21 · see citing works
- Authors
- Carneiro, A. M. D., Cook, E. H., Murphy, D. L., & Blakely, R. D.
- Affiliations
- Vanderbilt University (US)
- University of Illinois Chicago (US)
- National Institutes of Health (US)
- Corresponding author
- Blakely, Randy D.
- Venue
- Journal of Clinical Investigation
- Published
- 2008-04-01
- Volume
- 118
- Issue
- 4
- Pages
- 1544-1552
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2260909
- OpenAlex
- W2144374554
- Cited by
- 180
- References
- 50
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 10 · 2020: 3 · 2019: 13 · 2018: 10 · 2017: 14 · 2016: 9 · 2015: 9 · 2014: 14 · 2013: 13 · 2012: 14
- FWCI
- 9.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute of Mental Health (P50MH078028, MH078028, NIMH P50)
- National Institute on Drug Abuse (R01DA007390, DA007390)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U19-HD 35482, U19HD035482)
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- serotonin transporter, integrin αIIbβ3, platelet aggregation, serotonin release, vesicular monoamine transporter, fibrinogen, ADP-induced aggregation, thrombin-induced aggregation, hyperserotonemia, autism spectrum disorder, cardiovascular disease
- MeSH terms
- Alleles, Animals, Biological Transport, Blood Platelets, Cell Line, Cell Membrane, Humans, Platelet Aggregation, Protein Binding, Serotonin, Mice, Knockout, Platelet Glycoprotein GPIIb-IIIa Complex, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, Serotonin Plasma Membrane Transport Proteins, Mice, Protein Phosphatase 1, Protein Phosphatase 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review