SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation
Open accessAbstract
The synapse contains densely localized and interacting proteins that enable it to adapt to changing inputs. We describe a Ca2+-sensitive protein complex involved in the regulation of AMPA receptor synaptic plasticity. The complex is comprised of MUPPI, a multi-PDZ domain-containing protein; SynGAP, a synaptic GTPase-activating protein; and the Ca2+/calmodulin-dependent kinase CaMKII. In synapses of hippocampal neurons, SynGAP and CaMKII are brought together by direct physical interaction with the PDZ domains of MUPP1, and in this complex, SynGAP is phosphorylated. Ca2+CaM binding to CaMKII dissociates it from the MUPP1 complex, and Ca2+ entering via the NMDAR drives the dephosphorylation of SynGAP. Specific peptide-induced SynGAP dissociation from the MUPP1-CaMKII complex results in SynGAP dephosphorylation accompanied by P38 MAPK inactivation, potentiation of synaptic AMPA responses, and an increase in the number of AMPAR-containing clusters in hippocampal neuron synapses. siRNA-mediated SynGAP knockdown confirmed these results. These data implicate SynGAP in NMDAR- and CaMKII-dependent regulation of AMPAR trafficking.
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?
Disrupting SynGAP expression in dissociated hippocampal neurons can enhance or suppress dendritic spine function.
“In addition, disrupting SynGAP expression in dissociated hippocampal neurons can enhance dendritic spine function (Kim et al., 2005; Rumbaugh et al., 2006) or suppress it (Krapivinsky et al., 2004).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Krapivinsky et al., 2004
SynGAP shapes developmental synaptic function through its synaptic GAP activity, suppressing biochemical signaling cascades in dendritic spines that promote synapse growth and AMPA receptor insertion.
“Mechanistically, SynGAP shapes developmental synaptic function through its synaptic GAP activity, where it suppresses many biochemical signaling cascades within dendritic spines that promote growth of synapses and insertion of AMPARs (Kim et al., 2005; Krapivinsky et al., 2004; Rumbaugh et al., 2006).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Krapivinsky et al., 2004
SynGAP's broad action on dendritic spine signaling arises from its central location in the NMDAR complex and its promiscuous GAP domain that can regulate various small G-proteins.
“This broad action of SynGAP on dendritic spine signaling arises from its central location in the NMDAR complex (Kennedy et al., 2005) and its endowment with a promiscuous GAP domain that can regulate a variety of small G-proteins (Krapivinsky et al., 2004; Pena et al., 2008).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Krapivinsky et al., 2004
Cites
Domain Interaction Between NMDA Receptor Subunits and the Postsynaptic Density Protein PSD-95
Kornau, H., Schenker, L. T., Kennedy, M. B., & Seeburg, P. H. (1995) · Science · doi:10.1126/science.7569905 · Cited by 1,882 · see citing works
The molecular basis of CaMKII function in synaptic and behavioural memory
Lisman, J., Schulman, H., & Cline, H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn753 · Cited by 1,860 · see citing works
Hayashi, Y., Shi, S.-H., Esteban, J. A., Piccini, A., Poncer, J.-C., & Malinow, R. (2000) · Science · doi:10.1126/science.287.5461.2262 · Cited by 1,524 · see citing works
Rapid Spine Delivery and Redistribution of AMPA Receptors After Synaptic NMDA Receptor Activation
Shi, S.-H., Hayashi, Y., Petralia, R. S., Zaman, S. H., Wenthold, R. J., Svoboda, K., & Malinow, R. (1999) · Science · doi:10.1126/science.284.5421.1811 · Cited by 1,276 · see citing works
Proteomic analysis of NMDA receptor–adhesion protein signaling complexes
Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P., & Grant, S. G. N. (2000) · Nature Neuroscience · doi:10.1038/76615 · Cited by 1,194 · see citing works
PDZ Domains and the Organization of Supramolecular Complexes
Sheng, M., & Sala, C. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1 · Cited by 1,191 · see citing works
Doyle, D., Lee, A., Lewis, J. H., Kim, E., Sheng, M., & MacKinnon, R. (1996) · Cell · doi:10.1016/s0092-8674(00)81307-0 · Cited by 1,170 · see citing works
Lu, W.-Y., Man, H.-Y., Ju, W., Trimble, W., Macdonald, J., & Wang, Y.-T. (2001) · Neuron · doi:10.1016/s0896-6273(01)00194-5 · Cited by 978 · see citing works
Carlin, R. K., Grab, D. J., Cohen, R. S., & Siekevitz, P. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.86.3.831 · Cited by 788 · see citing works
Ras and Rap control AMPA receptor trafficking during synaptic plasticity
Zhu, J. J., Qin, Y., Zhao, M., Van Aelst, L., & Malinow, R. (2002) · Cell · doi:10.1016/s0092-8674(02)00897-8 · Cited by 769 · see citing works
Interaction with the NMDA receptor locks CaMKII in an active conformation
Bayer, K.-U., De Koninck, P., Leonard, A. S., Hell, J. W., & Schulman, H. (2001) · Nature · doi:10.1038/35081080 · Cited by 732 · see citing works
PDZ Domains: Structural Modules for Protein Complex Assembly
Hung, A. Y., & Sheng, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.r100065200 · Cited by 699 · see citing works
Role of AMPA Receptor Cycling in Synaptic Transmission and Plasticity
Lüscher, C., Xia, H., Beattie, E. C., Carroll, R. C., von Zastrow, M., Malenka, R. C., & Nicoll, R. A. (1999) · Neuron · doi:10.1016/s0896-6273(00)81119-8 · Cited by 692 · see citing works
Xu, G., Lin, B. K., Tanaka, K., Dunn, D. M., Wood, D. R., Gesteland, R. F., White, R. L., Weiss, R. B., & Tamanoi, F. (1990) · Cell · doi:10.1016/0092-8674(90)90149-9 · Cited by 681 · see citing works
SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family
Kim, J. H., Liao, D., Lau, L.-F., & Huganir, R. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)81008-9 · Cited by 634 · see citing works
A Synaptic Ras-GTPase Activating Protein (p135 SynGAP) Inhibited by CaM Kinase II
Chen, H.-J., Rojas-Soto, M., Oguni, A., & Kennedy, M. B. (1998) · Neuron · doi:10.1016/s0896-6273(00)80471-7 · Cited by 590 · see citing works
Brewer, G. J. (1995) · Journal of Neuroscience Research · doi:10.1002/jnr.490420510 · Cited by 546 · see citing works
The NMDA Receptor Is Coupled to the ERK Pathway by a Direct Interaction between NR2B and RasGRF1
Krapivinsky, G. B., Krapivinsky, L., Manasian, Y., Ivanov, A., Tyzio, R., Pellegrino, C., Ben‐Ari, Y., Clapham, D. E., & Medina, I. (2003) · Neuron · doi:10.1016/s0896-6273(03)00645-7 · Cited by 431 · see citing works
Self-citationLuo, J.-H., Wang, Y.-H., Yasuda, R., Dunah, A., & Wolfe, B. (1997) · Molecular Pharmacology · doi:10.1124/mol.51.1.79 · Cited by 427 · see citing works
Komiyama, N. H., Watabe, A. M., Carlisle, H. J., Porter, K., Charlesworth, P., Monti, J., Strathdee, D. J. C., O'Carroll, C. M., Martin, S. J., Morris, R. G. M., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-22-09721.2002 · Cited by 382 · see citing works
Penzes, P., Johnson, R. C., Sattler, R., Zhang, X., Huganir, R. L., Kambampati, V., Mains, R. E., & Eipper, B. A. (2001) · Neuron · doi:10.1016/s0896-6273(01)00193-3 · Cited by 378 · see citing works
Man, H., Wang, Q., Lu, W.-Y., Ju, W. H., Ahmadian, G., Liu, L., D’Souza, S. A., Wong, T. P., Taghibiglou, C., Lu, J., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00228-9 · Cited by 345 · see citing works
Identification of a specific lns(l,3,4,5)P4-binding protein as a member of the GAP1 family
Cullen, P. J., Hsuan, J. J., Truong, O., Letcher, A. J., Jackson, T., Dawson, A. P., & Irvine, R. F. (1995) · Nature · doi:10.1038/376527a0 · Cited by 295 · see citing works
AMPA receptor trafficking and long-term potentiation
Malinow, R. (2003) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2002.1233 · Cited by 248 · see citing works
The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity
Kim, J. H., Lee, H.-K., Takamiya, K., & Huganir, R. L. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01119.2003 · Cited by 240 · see citing works
Role of Unc51.1 and its binding partners in CNS axon outgrowthPreprint
Tomoda, T., Kim, J. H., Zhan, C., & Hatten, M. E. (2004) · Genes & Development · doi:10.1101/gad.1151204 · Cited by 191 · see citing works
Cloning and characterization of MUPP1, a novel PDZ domain protein
Ullmer, C., Schmuck, K., Figge, A., & Lübbert, H. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00141-0 · Cited by 187 · see citing works
Park, H.-O., Chant, J., & Herskowitz, I. (1993) · Nature · doi:10.1038/365269a0 · Cited by 185 · see citing works
Molecular mechanisms associated with long-term consolidation of the NMDA signals
Plátenı́k, J., Kuramoto, N., & Yoneda, Y. (2000) · Life Sciences · doi:10.1016/s0024-3205(00)00632-9 · Cited by 184 · see citing works
Poliak, S., Matlis, S., Ullmer, C., Scherer, S. S., & Peles, E. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200207050 · Cited by 182 · see citing works
Lau, L., Mammen, A. L., Ehlers, M., Kindler, S., Chung, W. J., Garner, C. C., & Huganir, R. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21622 · Cited by 177 · see citing works
Modulation of Cellular Function by TAT Mediated Transduction of Full Length Proteins
Wadia, J. S., & Dowdy, S. F. (2003) · Current Protein and Peptide Science · doi:10.2174/1389203033487289 · Cited by 164 · see citing works
Salojin, K. V., Zhang, J., & Delovitch, T. L. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.2.844 · Cited by 149 · see citing works
Zhang, M., Tochio, H., Zhang, Q., Mandal, P. K., & Li, M. (1999) · Nature Structural Biology · doi:10.1038/8216 · Cited by 149 · see citing works
Energetic Determinants of Internal Motif Recognition by PDZ Domains
Harris, B. Z., Hillier, B. J., & Lim, W. A. (2001) · Biochemistry · doi:10.1021/bi010142l · Cited by 130 · see citing works
KIMBER, W. A., Trinkle‐Mulcahy, L., Cheung, P., Deák, M., MARSDEN, L. J., Kieloch, A., Watt, S. A., Javier, R. T., Alex, G. R. A. Y., Downes, C. P., et al. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3610525 · Cited by 129 · see citing works
Oh, J. S., Manzerra, P., & Kennedy, M. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314109200 · Cited by 118 · see citing works
Rap-specific GTPase Activating Protein follows an Alternative Mechanism
Brinkmann, T., Daumke, O., Herbrand, U., Kühlmann, D., Stege, P., Ahmadian, M. R., & Wittinghofer, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109176200 · Cited by 77 · see citing works
Palsson, E. M., Popoff, M. R., Thelestam, M., & O'Neill, L. A. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.11.7818 · Cited by 75 · see citing works
Iida, N., Namikawa, K., Kiyama, H., Ueno, H., Nakamura, S., & Hattori, S. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-17-06459.2001 · Cited by 74 · see citing works
Parker, L. L., Backstrom, J. R., Sanders‐Bush, E., & Shieh, B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210973200 · Cited by 62 · see citing works
Characterization of a Novel synGAP Isoform, synGAP-β
Li, W., Okano, A., Tian, Q. B., Nakayama, K., Furihata, T., Nawa, H., & Suzuki, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010744200 · Cited by 61 · see citing works
Mancini, A., Koch, A., Stefan, M., Niemann, H., & Tamura, T. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)02036-6 · Cited by 52 · see citing works
Regulation of AMPA Receptor Activity, Synaptic Targeting and Recycling: Role in Synaptic Plasticity
Gomes, A. R., Correia, S. S., Carvalho, A. L., & Duarte, C. B. (2003) · Neurochemical Research · doi:10.1023/a:1025610122776 · Cited by 46 · see citing works
[35] Enzymology of GTPase acceleration in phototransduction
Cowan, C. W., Wensel, T. G., & Arshavsky, V. Y. (2000) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(00)15865-3 · Cited by 36 · see citing works
Expression of MUPP1 protein in mouse brain
Sitek, B., Poschmann, G., Schmidtke, K., Ullmer, C., Maskri, L., Andriske, M., Stichel, C. C., Zhu, X., & Luebbert, H. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02338-2 · Cited by 34 · see citing works
Pei, L., Teves, R. L., Wallace, M. C., & Gurd, J. W. (2001) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200108000-00008 · Cited by 23 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Clapham, D. E. (2007) · Cell · doi:10.1016/j.cell.2007.11.028 · Cited by 4,175 · see citing works
Self-citationMechanisms of CaMKII action in long-term potentiation
Lisman, J., Yasuda, R., & Raghavachari, S. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3192 · Cited by 1,134 · see citing works
Balancing Structure and Function at Hippocampal Dendritic Spines
Bourne, J. N., & Harris, K. M. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.060407.125646 · Cited by 916 · see citing works
Calmodulin-kinases: modulators of neuronal development and plasticity.
Wayman, G. A., Lee, Y.-S., Tokumitsu, H., Silva, A., & Soderling, T. R. (2008) · Neuron · doi:10.1016/j.neuron.2008.08.021 · Cited by 567 · see citing works
Molecular mechanisms underlying emotional learning and memory in the lateral amygdala
Rodrigues, S. M., Schafe, G. E., & LeDoux, J. E. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.014 · Cited by 491 · see citing works
Assémat, E., Bazellières, E., Pallesi‐Pocachard, E., Bivic, A. L., & Massey‐Harroche, D. (2007) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.08.029 · Cited by 471 · see citing works
Clement, J. P., Aceti, M., Creson, T. K., Ozkan, E. D., Shi, Y., Reish, N. J., Almonte, A. G., Miller, B. H., Wiltgen, B. J., Miller, C. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.045 · Cited by 385 · see citing works
Nakata, K., Abrams, B. S., Grill, B. J., Goncharov, A., Huang, X., Chisholm, A. D., & Jin, Y. (2005) · Cell · doi:10.1016/j.cell.2004.12.017 · Cited by 364 · see citing works
Mutations in <i>SYNGAP1</i> in Autosomal Nonsyndromic Mental Retardation
Hamdan, F. F., Gauthier, J., Spiegelman, D., Noreau, A., Yang, Y., Pellerin, S., Dobrzeniecka, S., Côté, M., Perreau-Linck, E., Carmant, L., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0805392 · Cited by 336 · see citing works
Spine architecture and synaptic plasticity
Carlisle, H. J., & Kennedy, M. B. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.01.008 · Cited by 351 · see citing works
Vosseller, K., Trinidad, J. C., Chalkley, R. J., Specht, C. G., Thalhammer, A., Lynn, A. J., Snedecor, J., Guan, S., Medzihradszky, K. F., Maltby, D. A., et al. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.t500040-mcp200 · Cited by 346 · see citing works
CaMKII regulation in information processing and storage
Coultrap, S. J., & Bayer, K. U. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.05.003 · Cited by 313 · see citing works
Integration of biochemical signalling in spines
Kennedy, M. B., Beale, H. C., Carlisle, H. J., & Washburn, L. R. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1685 · Cited by 286 · see citing works
Boudreau, A. C., Reimers, J. M., Milovanovic, M., & Wolf, M. E. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2163-07.2007 · Cited by 277 · see citing works
Araki, Y., Zeng, M., Zhang, M., & Huganir, R. L. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.023 · Cited by 271 · see citing works
Synaptic Signaling in Learning and Memory
Kennedy, M. B. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016824 · Cited by 270 · see citing works
Berryer, M. H., Hamdan, F. F., Klitten, L. L., Møller, R. S., Carmant, L., Schwartzentruber, J., Patry, L., Dobrzeniecka, S., Rochefort, D., Neugnot-Cerioli, M., et al. (2013) · Human Mutation · doi:10.1002/humu.22248 · Cited by 266 · see citing works
SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons
Rumbaugh, G., Adams, J. P., Kim, J. H., & Huganir, R. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600084103 · Cited by 260 · see citing works
Otmakhov, N., Tao-Cheng, J.-H., Carpenter, S., Asrican, B., Dosemeci, A., Reese, T. S., & Lisman, J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2350-04.2004 · Cited by 258 · see citing works
Role of the CaMKII/NMDA Receptor Complex in the Maintenance of Synaptic Strength
Sanhueza, M., Fernandez-Villalobos, G., Stein, I. S., Kasumova, G., Zhang, P., Bayer, K. U., Otmakhov, N., Hell, J. W., & Lisman, J. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1250-11.2011 · Cited by 248 · see citing works
Jones, K. A., Srivastava, D. P., Allen, J. A., Strachan, R. T., Roth, B. L., & Penzes, P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905884106 · Cited by 226 · see citing works
Current view on the functional regulation of the neuronal K+-Cl− cotransporter KCC2
Medina, I., Friedel, P., Rivera, C., Kahle, K. T., Kourdougli, N., Uvarov, P., & Pellegrino, C. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00027 · Cited by 203 · see citing works
Self-citationGenetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy
Mignot, C., von Stülpnagel, C., Nava, C., Ville, D. M., Sanlaville, D., Lesca, G., Rastetter, A., Gachet, B., Marie, Y., Korenke, G. C., et al. (2016) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103451 · Cited by 181 · see citing works
Tau exacerbates excitotoxic brain damage in an animal model of stroke
Bi, M., Gladbach, A., van Eersel, J., Ittner, A., Przybyla, M., van Hummel, A., Chua, S. W., van der Hoven, J., Lee, W. S., Müller, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00618-0 · Cited by 167 · see citing works
Twenty Years of SynGAP Research: From Synapses to Cognition
Gamache, T. R., Araki, Y., & Huganir, R. L. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.0420-19.2020 · Cited by 161 · see citing works
The dark side of opioids in pain management: basic science explains clinical observation
Rivat, C., & Ballantyne, J. (2016) · PAIN Reports · doi:10.1097/pr9.0000000000000570 · Cited by 160 · see citing works
Schmitt, J., Guire, E. S., Saneyoshi, T., & Soderling, T. R. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4086-04.2005 · Cited by 157 · see citing works
Functions of p38 MAP Kinases in the Central Nervous System
Asih, P. R., Prikas, E., Stefanoska, K., Tan, A. R. P., Ahel, H. I., & Ittner, A. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.570586 · Cited by 158 · see citing works
Specific Targeting of Pro-Death NMDA Receptor Signals with Differing Reliance on the NR2B PDZ Ligand
Soriano, F. X., Martel, M., Papadia, S., Vaslin, A., Baxter, P. S., Rickman, C., Forder, J. P., Tymianski, M., Duncan, R. R., Aarts, M. M., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1207-08.2008 · Cited by 156 · see citing works
Funk, A. J., McCullumsmith, R. E., Haroutunian, V. H., & Meador‐Woodruff, J. H. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.267 · Cited by 155 · see citing works
GTPase activating proteins: structural and functional insights 18 years after discovery
Scheffzek, K., & Ahmadian, M. R. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5136-x · Cited by 154 · see citing works
Activity-driven postsynaptic translocation of CaMKII
Merrill, M. A., Chen, Y., Strack, S., & Hell, J. W. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.10.003 · Cited by 148 · see citing works
Shonesy, B. C., Jalan‐Sakrikar, N., Cavener, V. S., & Colbran, R. J. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-420170-5.00003-9 · Cited by 134 · see citing works
SynGAP Regulates Steady-State and Activity-Dependent Phosphorylation of Cofilin
Carlisle, H. J., Manzerra, P., Marcora, E., & Kennedy, M. B. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4695-08.2008 · Cited by 128 · see citing works
Ye, X., & Carew, T. J. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.013 · Cited by 121 · see citing works
Santini, E., & Klann, E. (2014) · Science Signaling · doi:10.1126/scisignal.2005832 · Cited by 118 · see citing works
Jeyabalan, N., & Clement, J. P. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00032 · Cited by 118 · see citing works
Nakata, H., & Nakamura, S. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.04.041 · Cited by 117 · see citing works
CaMKIIβ Association with the Actin Cytoskeleton Is Regulated by Alternative Splicing
O'Leary, H., Lasda, E., & Bayer, K. U. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-03-0252 · Cited by 113 · see citing works
The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction
Pena, V., Hothorn, M., Eberth, A., Kaschau, N., Parret, A., Gremer, L., Bonneau, F., Ahmadian, M. R., & Scheffzek, K. (2008) · The EMBO Reports · doi:10.1038/embor.2008.20 · Cited by 101 · see citing works
PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways
Dunn, H. A., & Ferguson, S. S. G. (2015) · Molecular Pharmacology · doi:10.1124/mol.115.098509 · Cited by 108 · see citing works
Composition and function of the Crumbs protein complex in the mammalian retina
Gosens, I., den Hollander, A. I., Cremers, F. P. M., & Roepman, R. (2008) · Experimental Eye Research · doi:10.1016/j.exer.2008.02.005 · Cited by 108 · see citing works
Striatal Involvement in Human Alcoholism and Alcohol Consumption, and Withdrawal in Animal Models
Chen, G., Carlson, V. C. C., Wang, J., Beck, A., Heinz, A., Dorit Ron, A., Lovinger, D. M., & Buck, K. J. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01520.x · Cited by 98 · see citing works
Comprehensive behavioral analysis of heterozygous Syngap1 knockout mice
Nakajima, R., Takao, K., Hattori, S., Shoji, H., Komiyama, N. H., Grant, S. G. N., & Miyakawa, T. (2019) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12073 · Cited by 96 · see citing works
Novel insights into CaMKII function and regulation during memory formation
Lucchesi, W., Mizuno, K., & Giese, K.-P. (2010) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2010.10.009 · Cited by 95 · see citing works
Bengtson, C. P., & Bading, H. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-3-7091-0932-8_17 · Cited by 96 · see citing works
A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons
Lin, Y., Frei, J. A., Kilander, M. B. C., Shen, W., & Blatt, G. J. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00263 · Cited by 91 · see citing works
Lü, W., Isozaki, K., Roche, K. W., & Nicoll, R. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016289107 · Cited by 92 · see citing works
Adachi, M., Hamazaki, Y., Kobayashi, Y., Itoh, M., Tsukita, S., Furuse, M., & Tsukita, S. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01505-08 · Cited by 92 · see citing works
SynGAP isoforms exert opposing effects on synaptic strength
McMahon, A. C., Barnett, M. W., O'Leary, T. S., Stoney, P. N., Collins, M. O., Papadia, S., Choudhary, J. S., Komiyama, N. H., Grant, S. G. N., Hardingham, G. E., et al. (2012) · Nature Communications · doi:10.1038/ncomms1900 · Cited by 91 · see citing works
Regulation of AMPA receptor recruitment at developing synapses
Hall, B. J., & Ghosh, A. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2007.11.010 · Cited by 91 · see citing works
Species-conserved SYNGAP1 phenotypes associated with neurodevelopmental disorders
Kılınç, M., Creson, T. K., Rojas, C., Aceti, M., Ellegood, J., Vaissière, T., Lerch, J. P., & Rumbaugh, G. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.03.008 · Cited by 81 · see citing works
Ball, R. (2009) · Scientometrics · doi:10.1007/s11192-007-1984-5 · Cited by 88 · see citing works
GAP1 Family Members Constitute Bifunctional Ras and Rap GTPase-activating Proteins
Kupzig, S., Deaconescu, D., Bouyoucef, D., Walker, S. A., Liu, Q., Polte, C. L., Daumke, O., Ishizaki, T., Lockyer, P. J., Wittinghofer, A., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512802200 · Cited by 87 · see citing works
Funk, A. J., Rumbaugh, G., Harotunian, V., McCullumsmith, R. E., & Meador‐Woodruff, J. H. (2009) · Neuroreport · doi:10.1097/wnr.0b013e32832d30d9 · Cited by 85 · see citing works
Delint-Ramírez, I., Fernandez, E., Bayés, À., Kicsi, E., Komiyama, N., & Grant, S. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1792-10.2010 · Cited by 88 · see citing works
Wang, C.-C., Held, R. G., & Hall, B. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083941 · Cited by 84 · see citing works
Glutamatergic signaling in the brain's white matter
Bakiri, Y., Burzomato, V., Frugier, G., Hamilton, N. B., Káradóttir, R. T., & Attwell, D. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.015 · Cited by 83 · see citing works
Walkup, W. G., Washburn, L. R., Sweredoski, M. J., Carlisle, H. J., Graham, R. L., Hess, S. Y., & Kennedy, M. B. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.614420 · Cited by 77 · see citing works
GABAB Receptor Association with the PDZ Scaffold Mupp1 Alters Receptor Stability and Function
Balasubramanian, S., Fam, S. R., & Hall, R. A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607695200 · Cited by 82 · see citing works
Methods for proteomics in neuroscience
Tannu, N. S., & Hemby, S. E. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)58003-3 · Cited by 79 · see citing works
Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and InteractionsPreprint
Scheffzek, K., & Shivalingaiah, G. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031500 · Cited by 81 · see citing works
Nonredundant Functions for Ras GTPase-Activating Proteins in Tissue Homeostasis
King, P. D., Lubeck, B. A., & Lapinski, P. E. (2013) · Science Signaling · doi:10.1126/scisignal.2003669 · Cited by 80 · see citing works
Structural mechanisms of plexin signaling
Pascoe, H. G., Wang, Y., & Zhang, X. (2015) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2015.03.006 · Cited by 76 · see citing works
Waxman, E. A., & Lynch, D. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502080200 · Cited by 78 · see citing works
Srivastava, P., Dhuriya, Y. K., Kumar, V., Srivastava, A., Gupta, R., Shukla, R. K., Yadav, R. S., Dwivedi, H. N., Pant, A. B., & Khanna, V. K. (2018) · NeuroToxicology · doi:10.1016/j.neuro.2018.04.018 · Cited by 77 · see citing works
Jiménez-Gómez, A., Niu, S., Andujar-Perez, F., McQuade, E. A., Balasa, A., Huss, D., Coorg, R. K., Quach, M. M., Vinson, S. S., Risen, S., et al. (2019) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-019-9276-y · Cited by 76 · see citing works
SYNGAP1 mutations: Clinical, genetic, and pathophysiological features
Agarwal, M., Johnston, M. V., & Stafstrom, C. E. (2019) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2019.08.003 · Cited by 72 · see citing works
Muhia, M., Yee, B. K., Feldon, J., Markopoulos, F., & Knuesel, I. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07079.x · Cited by 71 · see citing works
Izumi, Y., Tokuda, K., & Zorumski, C. F. (2007) · Hippocampus · doi:10.1002/hipo.20383 · Cited by 73 · see citing works
Temporal Sensitivity of Protein Kinase A Activation in Late-Phase Long Term Potentiation
Kim, M., Huang, T., Abel, T., & Blackwell, K. T. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000691 · Cited by 72 · see citing works
Junctional adhesion molecule-A: functional diversity through molecular promiscuity
Steinbacher, T., Kummer, D., & Ebnet, K. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2729-0 · Cited by 72 · see citing works
Differential expression of PSD proteins in age-related spatial learning impairments
Nyffeler, M., Zhang, W., Feldon, J., & Knuesel, I. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.11.003 · Cited by 72 · see citing works
Evolution of the Ras-like small GTPases and their regulators
van Dam, T. J. P., Bos, J. L., & Snel, . (2011) · Small GTPases · doi:10.4161/sgtp.2.1.15113 · Cited by 70 · see citing works
Behavioral and Cerebellar Transmission Deficits in Mice Lacking the Autism-Linked Gene Islet Brain-2
Giza, J., Urbanski, M. J., Prestori, F., Bandyopadhyay, B., Yam, A., Friedrich, V., Kelley, K., D'Angelo, E., & Goldfarb, M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1161-10.2010 · Cited by 68 · see citing works
AGAP3 and Arf6 Regulate Trafficking of AMPA Receptors and Synaptic Plasticity
Oku, Y., & Huganir, R. L. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0341-13.2013 · Cited by 66 · see citing works
Genetics and genomics of alcohol sensitivity
Morozova, T. V., Mackay, T. F. C., & Anholt, R. R. H. (2014) · Molecular Genetics and Genomics · doi:10.1007/s00438-013-0808-y · Cited by 64 · see citing works
Dendritic spine actin cytoskeleton in autism spectrum disorder
Joensuu, M., Lanoue, V., & Hotulainen, P. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.08.023 · Cited by 65 · see citing works
Focus on HTR2C: A possible suggestion for genetic studies of complex disorders
Drago, A., & Serretti, A. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30864 · Cited by 63 · see citing works
Poddar, R., & Paul, S. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12102 · Cited by 63 · see citing works
Shi, G., Han, J., & Andres, D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507364200 · Cited by 62 · see citing works
Tang, V. (2006) · Biology Direct · doi:10.1186/1745-6150-1-37 · Cited by 66 · see citing works
Crumbs proteins in epithelial morphogenesis
Bazellières, E. (2009) · Frontiers in bioscience · doi:10.2741/3368 · Cited by 59 · see citing works
Regulation of Synapse Structure and Function by Distinct Myosin II Motors
Rubio, M. D., Johnson, R. C., Miller, C. A., Huganir, R. L., & Rumbaugh, G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3294-10.2011 · Cited by 57 · see citing works
Li, X., Penes, M. C., Odermatt, B., Willecke, K., & Nagy, J. I. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06431.x · Cited by 58 · see citing works
Sullivan, B. J., Ammanuel, S. G., Kipnis, P. A., Araki, Y., Huganir, R. L., & Kadam, S. D. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.12.025 · Cited by 57 · see citing works
Huang, G., Sun, Z.-L., Li, H., & Feng, D. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.01.007 · Cited by 54 · see citing works
A role for synGAP in regulating neuronal apoptosis
Knuesel, I., Elliott, A., Chen, H., Mansuy, I. M., & Kennedy, M. B. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03908.x · Cited by 54 · see citing works
The role of kisspeptin and GPR54 in the hippocampus
Arai, A. (2008) · Peptides · doi:10.1016/j.peptides.2008.07.023 · Cited by 54 · see citing works
Interplay of enzymatic and structural functions of Ca MKII in long‐term potentiation
Kim, K., Saneyoshi, T., Hosokawa, T., Okamoto, K., & Hayashi, Y. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13672 · Cited by 51 · see citing works
Synaptic Ras GTPase Activating Protein Regulates Pattern Formation in the Trigeminal System of Mice
Barnett, M. W., Watson, R. F., Vitalis, T., Porter, K., Komiyama, N. H., Stoney, P. N., Gillingwater, T. H., Grant, S. G. N., & Kind, P. C. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3164-05.2006 · Cited by 52 · see citing works
Neurofibromin Is the Major Ras Inactivator in Dendritic Spines
Oliveira, A. F., & Yasuda, R. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3096-13.2014 · Cited by 52 · see citing works
Lanaspa, M. A., Andrés-Hernando, A., Rivard, C. J., Dai, Y., & Berl, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805761105 · Cited by 52 · see citing works
Samudio‐Ruiz, S. L., Allan, A. M., Valenzuela, C. F., Perrone‐Bizzozero, N. I., & Caldwell, K. K. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06049.x · Cited by 52 · see citing works
Weldon, M., Kılınç, M., Holder, J. L., & Rumbaugh, G. (2018) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-018-9225-1 · Cited by 50 · see citing works
Mohanan, A. G., Gunasekaran, S., Jacob, R. S., & Omkumar, R. V. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.855752 · Cited by 57 · see citing works
Inhibition and Termination of Physiological Responses by GTPase Activating Proteins
Ligeti, E., Welti, S., & Scheffzek, K. (2012) · Physiological Reviews · doi:10.1152/physrev.00045.2010 · Cited by 51 · see citing works
Gou, G., Roca‐Fernández, A., Kılınç, M., Serrano, E., Reig‐Viader, R., Araki, Y., Huganir, R. L., de Quintana-Schmidt, C. J., Rumbaugh, G., & Bayés, À. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.14988 · Cited by 47 · see citing works
Zhao, Z., Liu, N., Huang, J., Lu, P., & Xu, X. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07160.x · Cited by 51 · see citing works
Li, X., Lynn, B. D., & Nagy, J. I. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07947.x · Cited by 50 · see citing works
- Authors
- Krapivinsky, G., Medina, I., Krapivinsky, L., Gapon, S., & Clapham, D. E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Inserm (FR)
- Corresponding author
- Clapham, David E
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 43
- Issue
- 4
- Pages
- 563-574
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2022174722
- Cited by
- 287
- References
- 47
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 19 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 12 · 2019: 11 · 2018: 18 · 2017: 12 · 2016: 13 · 2015: 13 · 2014: 16 · 2013: 9 · 2012: 16
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- SynGAP, MUPP1, CaMKII, p38 MAPK, NMDA receptor, AMPA receptor potentiation, synaptic plasticity, PDZ domain, AMPA receptor trafficking, hippocampal neurons, calcium/calmodulin signaling, synaptic protein complexes
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Hippocampus, Humans, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Synaptic Transmission, Synapses, Transfection, Receptors, N-Methyl-D-Aspartate, Calcium-Calmodulin-Dependent Protein Kinases, GTPase-Activating Proteins, ras GTPase-Activating Proteins, Mitogen-Activated Protein Kinases, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 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
