Arg kinase signaling in dendrite and synapse stabilization pathways: Memory, cocaine sensitivity, and stress

作者：Kerrisk Meghan E^*; Koleske Anthony J

来源：International Journal of Biochemistry & Cell Biology, 2013, 45(11): 2496-2500.

DOI：10.1016/j.biocel.2013.07.018

• lntegrin alpha 3 beta 1
• Actin cytoskeleton
• Neuronal stability
• Cocaine
• Corticosteroid

The AbI2/Arg nonreceptor tyrosine kinase is enriched in dendritic spines where it is essential for maintaining dendrite and synapse stability in the postnatal mouse brain. Arg is activated downstream of integrin alpha 3 beta 1 receptors and it regulates the neuronal actin cytoskeleton by directly binding F-actin and via phosphorylation of substrates including p190RhoGAP and cortactin. Neurons in mice lacking Arg or integrin alpha 3 beta 1 develop normally through postnatal day 21 (P21), however by P42 mice exhibit major reductions in dendrite arbor size and complexity, and lose dendritic spines and synapses. As a result, mice with loss of Arg and Arg-dependent signaling pathways have impairments in memory tasks, heightened sensitivity to cocaine, and vulnerability to corticosteroid-induced neuronal remodeling. Therefore, understanding the molecular mechanisms of Arg regulation may lead to therapeutic approaches to treat human psychiatric and neurodegenerative diseases in which neuronal structure is destabilized.

• 出版日期2013-11