title: Camkii-mediated phosphorylation regulates distributions of Syngap-α1 and -α2 at the postsynaptic density.
abstract: SynGAP, a protein abundant at the postsynaptic density (PSD) of glutamatergic neurons, is known to modulate synaptic strength by regulating the incorporation of AMPA receptors at the synapse. Two isoforms of SynGAP, α1 and α2, which differ in their C-termini, have opposing effects on synaptic strength. In the present study, antibodies specific for SynGAP-α1 and SynGAP-α2 are used to compare the distribution patterns of the two isoforms at the postsynaptic density (PSD) under basal and excitatory conditions. Western immunoblotting shows enrichment of both isoforms in PSD fractions isolated from adult rat brain. Immunogold electron microscopy of rat hippocampal neuronal cultures shows similar distribution of both isoforms at the PSD, with a high density of immunolabel within the PSD core under basal conditions. Application of NMDA promotes movement of SynGAP-α1 as well as SynGAP-α2 out of the PSD core. In isolated PSDs both isoforms of SynGAP can be phosphorylated upon activation of the endogenous CaMKII. Application of tatCN21, a cell-penetrating inhibitor of CaMKII, to hippocampal neuronal cultures blocks NMDA-induced redistribution of SynGAP-α1 and SynGAP-α2. Thus CaMKII activation promotes the removal of two distinct C-terminal SynGAP variants from the PSD.
authors: Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors: Yijung
authors: Y
authors: Yang
authors: Jung-Hwa
authors: JH
authors: Tao-Cheng
authors: K Ulrich
authors: KU
authors: Bayer
authors: Thomas S
authors: TS
authors: Reese
authors: Ayse
authors: A
authors: Dosemeci
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D004789:Enzyme Activation; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D057907:Post-Synaptic Density / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D013570:Synaptic Membranes / Q000378:metabolism
chemical_list: D002147:Calmodulin; D020690:GTPase-Activating Proteins; C112202:Syngap1 protein, rat; D016202:N-Methylaspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
references: J Biol Chem. 2010 Jul 2;285(27):20675-82
references: 20424167
references: Cold Spring Harb Perspect Biol. 2012 Jun 01;4(6):
references: 22510460
references: Mol Biol Cell. 2007 Dec;18(12):5024-33
references: 17942605
references: J Neurosci. 2004 Oct 6;24(40):8862-72
references: 15470153
references: Mol Cell Neurosci. 1998 Dec;12(6):363-75
references: 9888989
references: Neuron. 1998 May;20(5):895-904
references: 9620694
references: J Neurocytol. 2002 Sep-Nov;31(8-9):605-12
references: 14501202
references: J Neurosci. 2010 Jun 16;30(24):8214-20
references: 20554872
references: J Neurosci. 2000 May 1;20(9):3076-84
references: 10777771
references: Learn Mem. 2012 Jun 14;19(7):268-81
references: 22700469
references: Mol Cell Neurosci. 2005 Jul;29(3):436-52
references: 15894489
references: J Biol Chem. 2004 Apr 23;279(17):17980-8
references: 14970204
references: Cell. 2012 Nov 9;151(4):709-723
references: 23141534
references: Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4344-51
references: 16537406
references: Mol Cell Proteomics. 2006 Jun;5(6):1158-70
references: 16507876
references: Neuron. 1998 Apr;20(4):683-91
references: 9581761
references: Trends Neurosci. 2012 Oct;35(10):607-18
references: 22717267
references: Nat Rev Neurosci. 2004 Oct;5(10):771-81
references: 15378037
references: Neuropsychopharmacology. 2009 Jun;34(7):1659-72
references: 19145222
references: Eur J Neurosci. 2010 Feb;31(3):529-43
references: 20105235
references: Proc Natl Acad Sci U S A. 1992 May 15;89(10):4363-7
references: 1350090
references: Nat Commun. 2012 Jun 12;3:900
references: 22692543
references: Nat Rev Neurosci. 2012 Feb 15;13(3):169-82
references: 22334212
references: J Neurosci. 1993 Jul;13(7):2910-8
references: 8331379
references: Neuroscience. 2011 Sep 29;192:132-9
references: 21736925
references: J Neurosci. 2006 Feb 1;26(5):1355-65
references: 16452659
references: Biochem Biophys Res Commun. 2010 Jan 1;391(1):78-84
references: 19896464
references: Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10890-5
references: 9724800