Synaptic cross-talk between N-methyl-D-aspartate receptors and LAPSER1-beta-catenin at excitatory synapses.
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.
Schmeisser
Michael J
MJ
Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
Grabrucker
Andreas M
AM
Bockmann
Juergen
J
Boeckers
Tobias M
TM
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*
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
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