Molecular mechanism of strengthening synaptic connection by neural activity.

点击翻译按钮获取中文摘要

We investigated the role of activity-regulated adhesion molecule arcadlin. Arcadlin is synthesized in neurons and carried to synapses and may be involved in synaptic reorganization stimulated by synaptic activity. Here, we analyzed the interaction of TAO2 with the cytoplasmic region of Arcadlin. Homophilic binding of extracellular (EC) domains of arcadlin activated TAO2 and its down-stream kinases, MKK3 and p38 MAP kinase. The homophilic interaction also induced the internalization of arcadlin itself. This internalization was completely blocked by the co-expression of dominant-negative dynamin, indicating that arcadlin was internalized by clathrin-mediated endocytosis. The absence of MKK3 and p38 MARK resulted in a loss of arcadlin endocytosis. Moreover, p38 MARK inhibitor SB203580 also inhibited the endocytosis of arcadlin. These results suggest that TAO2, stimulated by homophilic binding of arcadlin EC domains, activates p38 MAP kinase pathway and induces the endocytosis of arcadlin. Thus, neural activity may play a role in changing the strength of synaptic connections by regulating the number of cell adhesion molecules on the surface of synaptic membranes.