1,945
Views
7
CrossRef citations to date
0
Altmetric
Brief Report - Commissioned

Anchoring high concentrations of SynGAP at postsynaptic densities via liquid-liquid phase separation

, ORCID Icon &
Pages 296-304 | Received 24 Jan 2017, Accepted 12 Apr 2017, Published online: 23 Jun 2017

References

  • Aceti M, Creson TK, Vaissiere T, Rojas C, Huang WC, Wang YX, Petralia RS, Page DT, Miller CA, Rumbaugh G. Syngap1 haploinsufficiency damages a postnatal critical period of pyramidal cell structural maturation linked to cortical circuit assembly. Biol Psychiatry 2015; 77:805-15; PMID:25444158; https://doi.org/10.1016/j.biopsych.2014.08.001
  • Araki Y, Zeng M, Zhang M, Huganir RL. Rapid dispersion of SynGAP from synaptic spines triggers AMPA receptor insertion and spine enlargement during LTP. Neuron 2015; 85:173-89; PMID:25569349; https://doi.org/10.1016/j.neuron.2014.12.023
  • Berryer MH, Chattopadhyaya B, Xing P, Riebe I, Bosoi C, Sanon N, Antoine-Bertrand J, Lévesque M, Avoli M, Hamdan FF. Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function. Nat Commun 2016; 7:133340; PMID:27827368; https://doi.org/10.1038/ncomms13340
  • Berryer MH, Hamdan FF, Klitten LL, Møller RS, Carmant L, Schwartzentruber J, Patry L, Dobrzeniecka S, Rochefort D, Neugnot‐Cerioli M. Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency. Human Mutation 2013; 34:385-94; PMID:23161826; https://doi.org/10.1002/humu.22248
  • Bos JL, Rehmann H, Wittinghofer A. GEFs and GAPs: critical elements in the control of small G proteins. Cell 2007; 129:865-77; PMID:17540168; https://doi.org/10.1016/j.cell.2007.05.018
  • Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat Genetics 2013; 45:825-30; PMID:23708187; https://doi.org/10.1038/ng.2646
  • Chen HJ, Rojas-Soto M, Oguni A, Kennedy MB. A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II. Neuron 1998; 20:895-904; PMID:9620694; https://doi.org/10.1016/S0896-6273(00)80471-7
  • Cherfils J, Zeghouf M. Regulation of small gtpases by gefs, gaps, and gdis. Physiological Rev 2013; 93:269-309; PMID:23303910; https://doi.org/10.1152/physrev.00003.2012
  • Chua J.J.E. Macromolecular complexes at active zones: integrated nano-machineries for neurotransmitter release. Cell Mol Life Sci 2014; 71:3903-16; PMID:24912984; https://doi.org/10.1007/s00018-014-1657-5
  • Clement JP, Aceti M, Creson TK, Ozkan ED, Shi Y, Reish NJ, Almonte AG, Miller BH, Wiltgen BJ, Miller CA, et al. Pathogenic SYNGAP1 mutations impair cognitive development by disrupting the maturation of dendritic spine synapses. Cell 2012; 151:709-23; PMID:23141534; https://doi.org/10.1016/j.cell.2012.08.045
  • Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg IC, Anckarsäter H. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genetics 2007; 39:25-7; PMID:17173049; https://doi.org/10.1038/ng1933
  • Gauthier J, Champagne N, Lafrenière RG, Xiong L, Spiegelman D, Brustein E, Lapointe M, Peng H, Côté M, Noreau A. De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proc Natl Acad Sci 2010; 107:7863-8; https://doi.org/10.1073/pnas.0906232107
  • Guo X, Hamilton PJ, Reish NJ, Sweatt JD, Miller CA, Rumbaugh G. Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of Schizophrenia. Neuropsychopharmacology 2009; 34:1659-72; PMID:19145222; https://doi.org/10.1038/npp.2008.223
  • Hamdan FF, Daoud H, Piton A, Gauthier J, Dobrzeniecka S, Krebs MO, Joober R, Lacaille JC, Nadeau A, Milunsky JM. De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism. Biol Psychiatry 2011; 69:898-901; PMID:21237447; https://doi.org/10.1016/j.biopsych.2010.11.015
  • Hamdan FF, Gauthier J, Spiegelman D, Noreau A, Yang Y, Pellerin S, Dobrzeniecka S, Côté M, Perreau-Linck E, Carmant L. Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation. N Engl J Med 2009; 360:599-605; PMID:19196676; https://doi.org/10.1056/NEJMoa0805392
  • Kim JH, Lee HK, Takamiya K, Huganir RL. The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity. J Neurosci 2003; 23:1119-24; PMID:12598599
  • Kim JH, Liao D, Lau LF, Huganir RL. SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family. Neuron 1998; 20:683-91; PMID:9581761; https://doi.org/10.1016/S0896-6273(00)81008-9
  • Komiyama NH, Watabe AM, Carlisle HJ, Porter K, Charlesworth P, Monti J, Strathdee DJC, O'Carroll CM, Martin SJ, Morris RGM. SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor. J Neurosci 2002; 22:9721-32; PMID:12427827
  • Krapivinsky G, Medina I, Krapivinsky L, Gapon S, Clapham DE. SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation. Neuron 2004; 43:563-74; PMID:15312654; https://doi.org/10.1016/j.neuron.2004.08.003
  • McMahon AC, Barnett MW, O'Leary TS, Stoney PN, Collins MO, Papadia S, Choudhary JS, Komiyama NH, Grant S.G.N, Hardingham GE. SynGAP isoforms exert opposing effects on synaptic strength. Nat Communications 2012; 3:900; PMID:22692543; https://doi.org/10.1038/ncomms1900
  • Mignot C, Von Stülpnagel C, Nava C, Ville D, Sanlaville D, Lesca G, Rastetter A, Gachet B, Marie Y, Korenke GC. Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy. J Medical Genetics 2016; 5:511-22; PMID:26989088; https://doi.org/10.1136/jmedgenet-2015-103451
  • Moon IS, Sakagami H, Nakayama J, Suzuki T. Differential distribution of synGAPα1 and synGAPβ isoforms in rat neurons. Brain Res 2008; 1241:62-75; PMID:18824155; https://doi.org/10.1016/j.brainres.2008.09.033
  • Ozkan ED, Creson TK, Kramár EA, Rojas C, Seese RR, Babyan AH, Shi Y, Lucero R, Xu X, Noebels JL. Reduced cognition in Syngap1 mutants is caused by isolated damage within developing forebrain excitatory neurons. Neuron 2014; 82:1317-33; PMID:24945774; https://doi.org/10.1016/j.neuron.2014.05.015
  • Palay SL. Synapses in the central nervous system. J Biophys Biochem Cytology 1956; 2:193; PMID:13357542; https://doi.org/10.1083/jcb.2.4.193
  • Parker MJ, Fryer AE, Shears DJ, Lachlan KL, McKee SA, Magee AC, Mohammed S, Vasudevan PC, Park SM, Benoit V. De novo, heterozygous, loss‐of‐function mutations in SYNGAP1 cause a syndromic form of intellectual disability. Am J Medical Genetics Part A 2015; 167:2231-7; https://doi.org/10.1002/ajmg.a.37189
  • Pena V, Hothorn M, Eberth A, Kaschau N, Parret A, Gremer L, Bonneau F, Ahmadian MR, Scheffzek K. The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction. EMBO Reports 2008; 9:350-5; PMID:18323856; https://doi.org/10.1038/embor.2008.20
  • Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet 2012; 380:1674-82; https://doi.org/10.1016/S0140-6736(12)61480-9
  • Redin C., Gérard B., Lauer J., Herenger Y., Muller J., Quartier A., Masurel-Paulet A., Willems M., Lesca G, El-Chehadeh S. Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. J Med Genet 2014; 51(11):724-36
  • Rumbaugh G, Adams JP, Kim JH, Huganir RL. SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons. Proc Natl Acad Sci U S A 2006; 103:4344-51; PMID:16537406; https://doi.org/10.1073/pnas.0600084103
  • Sheng M, Hoogenraad CC. The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu Rev Biochem 2007; 76:823-47; PMID:17243894; https://doi.org/10.1146/annurev.biochem.76.060805.160029
  • Shoubridge C, Tarpey PS, Abidi F, Ramsden SL, Rujirabanjerd S, Murphy JA, Boyle J, Shaw M, Gardner A, Proos A, et al. Mutations in the guanine nucleotide exchange factor gene IQSEC2 cause nonsyndromic intellectual disability. Nat Genet 2010; 42:486-8; PMID:20473311; https://doi.org/10.1038/ng.588
  • Tomoda T, Kim JH, Zhan C, Hatten ME. Role of Unc51. 1 and its binding partners in CNS axon outgrowth. Genes Dev 2004; 18:541-58; https://doi.org/10.1101/gad.1151204
  • Vazquez LE, Chen HJ, Sokolova I, Knuesel I, Kennedy MB. SynGAP regulates spine formation. J Neurosci 2004; 24:8862-72; PMID:15470153; https://doi.org/10.1523/JNEUROSCI.3213-04.2004
  • Vissers L.E.L.M, de Ligt J, Gilissen C, Janssen I, Steehouwer M, de Vries P, van Lier B, Arts P, Wieskamp N, del Rosario M. A de novo paradigm for mental retardation. Nat Genetics 2010; 42:1109-12; PMID:21076407; https://doi.org/10.1038/ng.712
  • Volk L, Chiu SL, Sharma K, Huganir RL. Glutamate synapses in human cognitive disorders. Annual Rev Neurosci 2015; 38:127-49; PMID:25897873; https://doi.org/10.1146/annurev-neuro-071714-033821
  • Walkup Iv WG, Mastro TL, Schenker LT, Vielmetter J, Hu R, Iancu A, Reghunathan M, Bannon BD, Kennedy MB. A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain'Slots' in the postsynaptic density. Elife 2016; 5:e16813; PMID:27623146
  • Walkup WG, Washburn L, Sweredoski MJ, Carlisle HJ, Graham RL, Hess S, Kennedy MB. Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases. J Biol Chem 2015; 290:4908-27; PMID:25533468; https://doi.org/10.1074/jbc.M114.614420
  • Wang Y, He H, Srivastava N, Vikarunnessa S, Chen Yb, Jiang J, Cowan CW, Zhang X. Plexins are GTPase activating proteins for rap and are activated by induced dimerization. Sci Signal 2012; 5:ra6; PMID:22253263
  • Yang Y, Tao-Cheng JH, Bayer KU, Reese TS, Dosemeci A. Camkii-Mediated Phosphorylation regulates distributions of Syngap-α1 and–α2 at the Postsynaptic density. PloS One 2013; 8:e71795; PMID:23967245; https://doi.org/10.1371/journal.pone.0071795
  • Zeng M, Shang Y, Araki Y, Guo T, Huganir RL, Zhang M. Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity. Cell 2016; 166:1163-75; PMID:27565345; https://doi.org/10.1016/j.cell.2016.07.008
  • Zhou Y, Kaiser T, Monteiro P, Zhang X, Van der Goes MS, Wang D, Barak B, Zeng M, Li C, Lu C. Mice with Shank3 mutations associated with ASD and schizophrenia display both shared and distinct defects. Neuron 2016; 89:147-62; PMID:26687841; https://doi.org/10.1016/j.neuron.2015.11.023

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.