title: ProSAP1 and membrane nanodomain-associated syndapin I promote postsynapse formation and function.
abstract: Insights into mechanisms coordinating membrane remodeling, local actin nucleation, and postsynaptic scaffolding during postsynapse formation are important for understanding vertebrate brain function. Gene knockout and RNAi in individual neurons reveal that the F-BAR protein syndapin I is a crucial postsynaptic coordinator in formation of excitatory synapses. Syndapin I deficiency caused significant reductions of synapse and dendritic spine densities. These syndapin I functions reflected direct, SH3 domain-mediated associations and functional interactions with ProSAP1/Shank2. They furthermore required F-BAR domain-mediated membrane binding. Ultra-high-resolution imaging of specifically membrane-associated, endogenous syndapin I at membranes of freeze-fractured neurons revealed that membrane-bound syndapin I preferentially occurred in spines and formed clusters at distinct postsynaptic membrane subareas. Postsynaptic syndapin I deficiency led to reduced frequencies of miniature excitatory postsynaptic currents, i.e., to defects in synaptic transmission phenocopying ProSAP1/Shank2 knockout, and impairments in proper synaptic ProSAP1/Shank2 distribution. Syndapin I-enriched membrane nanodomains thus seem to be important spatial cues and organizing platforms, shaping dendritic membrane areas into synaptic compartments.
authors.affiliation: Institute for Biochemistry I, 2 Institute for Human Genetics, and 3 Electron Microscopy Center, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schneider
authors.forename: Eric
authors.initials: E
authors.lastname: Seemann
authors.forename: Lutz
authors.initials: L
authors.lastname: Liebmann
authors.forename: Rashmi
authors.initials: R
authors.lastname: Ahuja
authors.forename: Dennis
authors.initials: D
authors.lastname: Koch
authors.forename: Martin
authors.initials: M
authors.lastname: Westermann
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kessels
authors.forename: Britta
authors.initials: B
authors.lastname: Qualmann
mesh_terms: D000818:Animals; D003712:Dendrites; D057809:HEK293 Cells; D006801:Humans; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D055366:Synaptic Potentials / Q000502:physiology; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C508241:SDC1 protein, human; C122162:SHANK2 protein, human; C508242:Sdc1 protein, mouse; C488222:Shank2 protein, mouse; D053668:Syndecan-1
references.citation: Dev Cell. 2005 Dec;9(6):791-804
references.pmid: 16326391
references.citation: EMBO J. 2011 Sep 16;30(24):4955-69
references.pmid: 21926968
references.citation: J Neurosci. 1999 Aug 1;19(15):6506-18
references.pmid: 10414979
references.citation: Methods Cell Biol. 2008;88:181-204
references.pmid: 18617035
references.citation: J Neurosci. 2011 May 18;31(20):7300-11
references.pmid: 21593314
references.citation: Mol Biol Cell. 2010 Jan 1;21(1):165-76
references.pmid: 19889835
references.citation: J Cell Sci. 1995 Nov;108 ( Pt 11):3443-9
references.pmid: 8586656
references.citation: J Neurosci. 2003 Dec 17;23(37):11759-69
references.pmid: 14684878
references.citation: Nature. 2012 Jun 13;486(7402):261-5
references.pmid: 22699620
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12700-5
references.pmid: 19549836
references.citation: J Neurosci. 2004 Mar 10;24(10):2481-95
references.pmid: 15014124
references.citation: Nat Neurosci. 2006 May;9(5):611-21
references.pmid: 16617342
references.citation: Nature. 2012 Apr 29;486(7402):256-60
references.pmid: 22699619
references.citation: Nat Neurosci. 2006 Jun;9(6):752-60
references.pmid: 16648848
references.citation: Hum Mol Genet. 2012 Jan 15;21(2):344-57
references.pmid: 21994763
references.citation: EMBO J. 2002 Nov 15;21(22):6083-94
references.pmid: 12426380
references.citation: Cell. 2007 Oct 19;131(2):337-50
references.pmid: 17956734
references.citation: J Neurosci. 2008 Feb 13;28(7):1697-708
references.pmid: 18272690
references.citation: J Biol Chem. 2013 Mar 29;288(13):9303-12
references.pmid: 23420842
references.citation: Nature. 2011 Apr 28;472(7344):437-42
references.pmid: 21423165
references.citation: J Cell Biol. 2001 Apr 16;153(2):351-66
references.pmid: 11309416
references.citation: EMBO J. 2011 Feb 2;30(3):569-81
references.pmid: 21217644
references.citation: J Neurosci. 2012 Dec 5;32(49):17842-56
references.pmid: 23223303
references.citation: Histochem Cell Biol. 2012 Aug;138(2):215-30
references.pmid: 22718246
references.citation: J Cell Biol. 1998 Jul 27;142(2):499-509
references.pmid: 9679147
references.citation: J Microsc. 1990 Jun;158(Pt 3):365-78
references.pmid: 2395171
references.citation: J Cell Biol. 2000 Mar 6;148(5):1047-62
references.pmid: 10704453
references.citation: J Neurosci. 2011 Feb 16;31(7):2447-60
references.pmid: 21325512
references.citation: J Neurosci. 2008 Apr 9;28(15):3925-33
references.pmid: 18400891
references.citation: J Cell Sci. 2013 Jan 1;126(Pt 1):196-208
references.pmid: 23203810
references.citation: J Neurosci. 2008 Oct 1;28(40):10031-44
references.pmid: 18829961
references.citation: J Cell Sci. 2012 Aug 1;125(Pt 15):3578-89
references.pmid: 22467854
references.citation: Mol Biol Cell. 2005 Aug;16(8):3642-58
references.pmid: 15930129
references.citation: J Neurosci. 2009 Oct 21;29(42):13315-27
references.pmid: 19846719
references.citation: EMBO J. 2011 Jul 01;30(15):3147-59
references.pmid: 21725280
references.citation: Curr Opin Neurobiol. 2006 Feb;16(1):95-101
references.pmid: 16361095
references.citation: Mol Biol Cell. 2000 Jan;11(1):393-412
references.pmid: 10637315
references.citation: EMBO J. 2011 Aug 31;30(17):3501-15
references.pmid: 21878992
references.citation: J Biol Chem. 2006 May 12;281(19):13285-13299
references.pmid: 16540475
references.citation: Mol Biol Cell. 1999 Feb;10(2):501-13
references.pmid: 9950691
references.citation: Biochem Biophys Res Commun. 1999 Oct 14;264(1):247-52
references.pmid: 10527873