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Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2beta and p38 MAP kinases.

Authors: 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 
Citation: Yasuda S, etal., Neuron. 2007 Nov 8;56(3):456-71. doi: 10.1016/j.neuron.2007.08.020.
Pubmed: (View Article at PubMed) PMID:17988630
DOI: Full-text: 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 TAO2beta, 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. TAO2beta is a MAPKKK that activates the MEK3 MAPKK, which phosphorylates the p38 MAPK. Activation of p38 feeds-back on TAO2beta, 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/TAO2beta/MEK3/p38 provides a molecular mechanism for transducing neuronal activity into changes in synaptic morphologies.

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RGD Object Information
RGD ID: 13702360
Created: 2018-07-18
Species: All species
Last Modified: 2018-07-18
Status: ACTIVE



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