PKD1 Promotes Functional Synapse Formation Coordinated with N-Cadherin in Hippocampus.

Autor: Cheng Cen, Li-Da Luo, Wen-Qi Li, Gang Li, Na-Xi Tian, Ge Zheng, Dong-Min Yin, Yimin Zou, Yun Wang
Předmět:
Zdroj: Journal of Neuroscience; 1/3/2018, Vol. 38 Issue 1, p183-199, 17p
Abstrakt: 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 PKD 1 regulating the surface localization of N-cadherin and suggests that the PKD 1-N-cadherin interaction is critical for synapse formation and function. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index