TY - JOUR
T1 - Synaptic cross-talk between N-methyl-D-aspartate receptors and LAPSER1-β-catenin at excitatory synapses
AU - Schmeisser, Michael J.
AU - Grabrucker, Andreas M.
AU - Bockmann, Juergen
AU - Boeckers, Tobias M.
PY - 2009/10/16
Y1 - 2009/10/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70350357210&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.020628
DO - 10.1074/jbc.M109.020628
M3 - Article
C2 - 19703901
AN - SCOPUS:70350357210
SN - 0021-9258
VL - 284
SP - 29146
EP - 29157
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 42
ER -