2013 Fiscal Year Final Research Report

The analysis of molecular mechanism of Dock family protein in neurons

Research Project

Project/Area Number	24700392
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Neurochemistry/Neuropharmacology
Research Institution	Tokyo Metropolitan Institute of Medical Science
Principal Investigator	WATANABE Hayaki 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 研究員 (70595587)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	Dock3 / 緑内障 / アクチン
Research Abstract	Dock3, a new member of the guanine nucleotide exchange factor family, causes cellular morphological changes by activating the small GTPase Rac1. Overexpression of Dock3 in neural cells promotes neurite outgrowth through the formation of a protein complex with Fyn and WAVE downstream of brain-derived neurotrophic factor (BDNF) signaling. we found a novel Dock3-mediated BDNF pathway for neurite outgrowth. Dock3 forms a complex with Elmo and activated RhoG downstream of BDNF-TrkB signaling and induces neurite outgrowth via Rac1 activation in PC12 cells. In addition, Dock3 phosphorylation in Rac1 activation is important. We found that two key events that are necessary for efficient Dock3 phosphorylation, membrane recruitment of Dock3 and interaction of Dock3 with Elmo. These results suggest that Dock3 plays important roles downstream of BDNF signaling in the central nervous system where it stimulates actin polymerization by multiple pathways.