Synaptic cross-talk between N-methyl-D-aspartate receptors and LAPSER1-β-catenin at excitatory synapses

Michael J. Schmeisser, Andreas M. Grabrucker, Juergen Bockmann, Tobias M. Boeckers

Research output: Contribution to journalArticlepeer-review

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 β-catenin. Upon N-methyl-D-aspartate receptor-dependent activation, LAPSER1 and β-catenin comigrate from the postsynaptic density to the nucleus and induce the transcription and translation of known β-catenin target genes, including Tcfe2a and c-Myc. The nuclear export and cytoplasmic redistribution of β-catenin is tightly regulated by LAPSER1. We postulate a postsynaptic cross-talk between N-methyl-D-aspartate receptors and a LAPSER1-β-catenin complex that results in a self-regulated, synaptic activity-dependent expression of β-catenin target genes. This calls for a novel role of Tcfe2a and c-Myc in plastic changes of neural tissue.

Original languageEnglish
Pages (from-to)29146-29157
Number of pages12
JournalJournal of Biological Chemistry
Volume284
Issue number42
DOIs
Publication statusPublished - 16 Oct 2009
Externally publishedYes

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