title: Synaptic cross-talk between N-methyl-D-aspartate receptors and LAPSER1-beta-catenin at excitatory synapses.
abstract: Memory formation in the brain is thought to be depending upon long lasting plastic changes of synaptic contacts that require alterations on the transcriptional level. Here, we characterize LAPSER1, a putative cytokinetic tumor suppressor that binds directly to ProSAP2/Shank3 and the synaptic Rap-Gap protein SPAR1 as a novel postsynaptic density component. Postsynaptic LAPSER1 is in complex with all important members of the canonical Wnt pathway including beta-catenin. Upon N-methyl-D-aspartate receptor-dependent activation, LAPSER1 and beta-catenin comigrate from the postsynaptic density to the nucleus and induce the transcription and translation of known beta-catenin target genes, including Tcfe2a and c-Myc. The nuclear export and cytoplasmic redistribution of beta-catenin is tightly regulated by LAPSER1. We postulate a postsynaptic cross-talk between N-methyl-D-aspartate receptors and a LAPSER1-beta-catenin complex that results in a self-regulated, synaptic activity-dependent expression of beta-catenin target genes. This calls for a novel role of Tcfe2a and c-Myc in plastic changes of neural tissue.
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schmeisser
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Grabrucker
authors.forename: Juergen
authors.initials: J
authors.lastname: Bockmann
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry*; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry*; D009474:Neurons / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000378:metabolism; D013569:Synapses; D025521:Tumor Suppressor Proteins / Q000737:chemistry*; D020798:Two-Hybrid System Techniques; D051176:beta Catenin / Q000737:chemistry*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C440108:LZTS2 protein, human; D016271:Proto-Oncogene Proteins c-myc; D016194:Receptors, N-Methyl-D-Aspartate; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D002118:Calcium
references.citation: Cancer Res. 2007 Jun 1;67(11):5061-3
references.pmid: 17545579
references.citation: Nature. 2003 Apr 10;422(6932):583-8
references.pmid: 12660735
references.citation: J Neurosci. 2007 Aug 1;27(31):8334-43
references.pmid: 17670980
references.citation: J Neurosci. 2002 Feb 1;22(3):757-65
references.pmid: 11826105
references.citation: PLoS Biol. 2008 Feb;6(2):e34
references.pmid: 18303947
references.citation: Nature. 2000 Sep 28;407(6803):530-5
references.pmid: 11029007
references.citation: Oncogene. 2006 Dec 4;25(57):7545-53
references.pmid: 17143299
references.citation: Cell. 2005 Dec 2;123(5):903-15
references.pmid: 16325583
references.citation: Nat Neurosci. 2007 Apr;10(4):427-35
references.pmid: 17334360
references.citation: Synapse. 2007 Oct;61(10):866-8
references.pmid: 17623831
references.citation: Mol Cell Biol. 2001 Feb;21(3):691-702
references.pmid: 11154257
references.citation: Nature. 2005 Oct 27;437(7063):1370-5
references.pmid: 16251967
references.citation: Neuron. 2001 Aug 2;31(2):289-303
references.pmid: 11502259
references.citation: Cell. 2000 Mar 3;100(5):525-35
references.pmid: 10721990
references.citation: Nature. 2005 Aug 25;436(7054):1166-73
references.pmid: 16121183
references.citation: J Neurochem. 2002 Jun;81(5):903-10
references.pmid: 12065602
references.citation: J Biol Chem. 2002 Jan 25;277(4):2897-907
references.pmid: 11717310
references.citation: Neuron. 2008 Mar 13;57(5):705-18
references.pmid: 18341991
references.citation: Nat Rev Neurosci. 2003 Feb;4(2):113-20
references.pmid: 12563282
references.citation: Nat Rev Genet. 2004 Sep;5(9):691-701
references.pmid: 15372092
references.citation: J Cell Sci. 2000 Jun;113 ( Pt 11):1851-6
references.pmid: 10806096
references.citation: Curr Opin Neurobiol. 2003 Jun;13(3):354-65
references.pmid: 12850221
references.citation: Science. 2006 Feb 17;311(5763):1008-12
references.pmid: 16484497
references.citation: Nat Rev Neurosci. 2005 May;6(5):351-62
references.pmid: 15832199
references.citation: J Biol Chem. 2006 May 12;281(19):13805-13816
references.pmid: 16522626
references.citation: Mol Cell Biol. 2006 Dec;26(23):8857-67
references.pmid: 17000760
references.citation: Genes Dev. 2002 Oct 15;16(20):2699-712
references.pmid: 12381668
references.citation: J Cell Sci. 2002 Dec 1;115(Pt 23):4695-706
references.pmid: 12415013
references.citation: Nature. 2000 Sep 28;407(6803):527-30
references.pmid: 11029006
references.citation: EMBO J. 2007 Mar 7;26(5):1397-409
references.pmid: 17304222
references.citation: J Biol Chem. 1998 Aug 14;273(33):21324-31
references.pmid: 9694893
references.citation: Cell Tissue Res. 2006 Nov;326(2):409-22
references.pmid: 16865346
references.citation: Curr Opin Neurobiol. 2005 Feb;15(1):73-80
references.pmid: 15721747
references.citation: J Biol Chem. 2006 Apr 28;281(17):11910-6
references.pmid: 16501258
references.citation: J Neurochem. 2008 Jan;104(1):187-201
references.pmid: 17961154
references.citation: Trends Neurosci. 2007 Jun;30(6):268-75
references.pmid: 17467065
references.citation: Oncogene. 2001 Oct 11;20(46):6707-17
references.pmid: 11709705
references.citation: J Exp Biol. 1999 Nov;202(Pt 21):2887-91
references.pmid: 10518471
references.citation: Neuron. 2004 Sep 30;44(1):59-73
references.pmid: 15450160
references.citation: J Cell Sci. 2007 Feb 15;120(Pt 4):586-95
references.pmid: 17244647
references.citation: Cell. 2004 Feb 6;116(3):467-79
references.pmid: 15016380
references.citation: EMBO J. 2006 Jun 21;25(12):2723-34
references.pmid: 16724113
references.citation: Curr Opin Genet Dev. 2007 Feb;17(1):45-51
references.pmid: 17208432
references.citation: Annu Rev Cell Dev Biol. 2004;20:781-810
references.pmid: 15473860
references.citation: Neuron. 2002 Jul 3;35(1):91-105
references.pmid: 12123611
references.citation: Nat Rev Neurosci. 2002 Dec;3(12):921-31
references.pmid: 12461549
references.citation: FASEB J. 2007 Jul;21(9):2086-100
references.pmid: 17351128
references.citation: Trends Cell Biol. 2005 Apr;15(4):216-21
references.pmid: 15817378
references.citation: FEBS J. 2007 Jul;274(13):3218-23
references.pmid: 17565597
references.citation: Biosci Rep. 2005 Oct-Dec;25(5-6):309-27
references.pmid: 16307379
references.citation: Nat Genet. 2007 Jan;39(1):25-7
references.pmid: 17173049
references.citation: Trends Biochem Sci. 2006 Jul;31(7):366-73
references.pmid: 16793273
references.citation: Neuron. 2007 Feb 1;53(3):387-97
references.pmid: 17270735
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10374-9
references.pmid: 11504921
references.citation: Dev Cell. 2007 Mar;12(3):335-47
references.pmid: 17336901
references.citation: Mol Cell Neurosci. 2003 Jun;23(2):279-91
references.pmid: 12812759