Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

• 作者: Jin Zheng Lun Suo Yuxiao Zhou Liling Jia Jingwei Li Yanping Kuang Donghong Cui Xuehong Zhang Qiang Wu
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2021,（11）
• 所属期刊栏目: Articles
• 页码范围: 808-821
• 页数: 14页
• 语种: 英文
• DOI: 10.1093/jmcb/mjab057

摘要

Clustered protocadherins (Pcdhs) are a large family of cadherin-like cell adhesion proteins that are central for neurite self-avoidance and neuronal connectivity in the brain.Their downstream nonreceptor tyrosine kinase Pyk2 (proline-rich tyrosine ki-nase 2,also known as Ptk2b,Cakb,Raftk,Fak2,and Cadtk) is predominantly expressed in the hippocampus.We constructed Pyk2-null mouse lines and found that these mutant mice showed enhancement in contextual fear memory,without significant change in auditory-cued and spatial-referenced learning and memory.In addition,by preparing Y402F mutant mice,we observed that Pyk2 suppressed contextual fear memory in an autophosphorylation-independent manner.Moreover,using high-throughput RNA sequencing,we found that immediate early genes,such as Npas4,cFos,Zif268/Egr1,Arc,and Nr4a1,were enhanced in Pyk2-null mice.We further showed that Pyk2 disruption affected pyramidal neuronal complexity and spine dynamics.Thus,we demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2-null mice provide a model for understanding feat-related disorders.These findings have interesting implications regarding dysregulation of the Pcdh-Pyk2 axis in neuropsychiat-tic disorders.