N-Cadherin Regulates Cytoskeletally Associated IQGAP1/ERK Signaling and Memory Formation


Cadherin-mediated interactions are integral to synapse formation and potentiation. Here we show that N-cadherin is required for memory formation and regulation of a subset of underlying biochemical processes. N-cadherin antagonistic peptide containing the His-Ala-Val motif (HAV-N) transiently disrupted hippocampal N-cadherin dimerization and impaired the formation of long-term contextual fear memory while sparing short-term memory, retrieval, and extinction. HAV-N impaired the learning-induced phosphorylation of a distinctive, cytoskeletally associated fraction of hippocampal Erk-1/2 and altered the distribution of IQGAP1, a scaffold protein linking cadherin-mediated cell adhesion to the cytoskeleton. This effect was accompanied by reduction of N-cadherin/IQGAP1/Erk-2 interactions. Similarly, in primary neuronal cultures, HAV-N prevented NMDA-induced dendritic Erk-1/2 phosphorylation and caused relocation of IQGAP1 from dendritic spines into the shafts. The data suggest that the newly identified role of hippocampal N-cadherin in memory consolidation may be mediated, at least in part, by cytoskeletal IQGAP1/Erk signaling.

DOI: 10.1016/j.neuron.2007.07.034

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@article{Schrick2007NCadherinRC, title={N-Cadherin Regulates Cytoskeletally Associated IQGAP1/ERK Signaling and Memory Formation}, author={Christina Schrick and Andr{\'e} Fischer and Deepak P Srivastava and Natalie C Tronson and Peter Penzes and Jelena Radulovic}, journal={Neuron}, year={2007}, volume={55}, pages={786-798} }