Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2 beta and p38 MAP kinases

作者：Yasuda Shin; Tanaka Hidekazu^*; Sugiura Hiroko; Okamura Ko; Sakaguchi Taiki; Tran Uyen; Takemiya Takako; Mizoguchi Akira; Yagita Yoshiki; Sakurai Takeshi; De Robertis E M; Yamagata Kanato

来源：Neuron, 2007, 56(3): 456-471.

DOI：10.1016/j.neuron.2007.08.020

Synaptic activity induces changes in the number of dendritic spines. Here, we report a pathway of regulated endocytosis triggered by arcadlin, a protocadherin induced by electroconvulsive and other excitatory stimuli in hippocampal neurons. The homophilic binding of extracellular arcadlin domains activates TAO2 beta, a splice variant of the thousand and one amino acid protein kinase 2, cloned here by virtue of its binding to the arcadlin intracellular domain. TAO2 beta is a MAPKKK that activates the MEK3 MAPKK, which phosphorylates the p38 MAPK Activation of p38 feeds-back on TAO2 beta, phosphorylating a key serine required for triggering endocytosis of N-cadherin at the synapse. Arcadlin knockout increases the number of dendritic spines, and the phenotype is rescued by siRNA knockdown of N-cadherin. This pathway of regulated endocytosis of N-cadherin via protocadherin/TAO2 beta/ MEK3/p38 provides a molecular mechanism for transducing neuronal activity into changes in synaptic morphologies.

• 出版日期2007-11-8