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.