Abstract:
: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.
journal_name
Neuronjournal_title
Neuronauthors
Yasuda S,Tanaka H,Sugiura H,Okamura K,Sakaguchi T,Tran U,Takemiya T,Mizoguchi A,Yagita Y,Sakurai T,De Robertis EM,Yamagata Kdoi
10.1016/j.neuron.2007.08.020subject
Has Abstractpub_date
2007-11-08 00:00:00pages
456-71issue
3eissn
0896-6273issn
1097-4199pii
S0896-6273(07)00663-0journal_volume
56pub_type
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