pkd1 promotes functional synapse formation coordinated with n-cadherin in hippocampus

Functional synapse formation is critical for the wiring of neural circuits in the developing brain. the cell adhesion molecule n-cadherin plays important roles in target recognition and synaptogenesis. however, the molecular mechanisms that regulate the localization of n-cadherin and the subsequent effects remain poorly understood. here, we show that protein kinase d1 (pkd1) directly binds to n-cadherin at amino acid residues 836–871 and phosphorylates it at ser 869, 871, and 872, thereby increasing the surface localization of n-cadherin and promoting functional synapse formation in primary cultured hippocampal neurons obtained from embryonic day 18 rat embryos of either sex. intriguingly, neuronal activity enhances the interactions between n-cadherin and pkd1, which are critical for the activity-dependent growth of dendritic spines. accordingly, either disruption the binding between n-cadherin and pkd1 or preventing the phosphorylation of n-cadherin by pkd1 in the hippocampal ca1 region of male rat leads to the reduction in synapse number and impairment of ltp. together, this study demonstrates a novel mechanism of pkd1 regulating the surface localization of n-cadherin and suggests that the pkd1-n-cadherin interaction is critical for synapse formation and function.