The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
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.
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“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]
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Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene
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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 874
The serotonin system in autism spectrum disorder: From biomarker to animal models
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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
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 288
Metadata
- 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
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