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Dock3 regulates BDNF ‐ T rk B signaling for neurite outgrowth by forming a ternary complex with E lmo and R ho G
Author(s) -
Namekata Kazuhiko,
Watanabe Hayaki,
Guo Xiaoli,
Kittaka Daiji,
Kawamura Kazuto,
Kimura Atsuko,
Harada Chikako,
Harada Takayuki
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2012.01616.x
Subject(s) - neurite , guanine nucleotide exchange factor , microbiology and biotechnology , rac1 , biology , gtpase , phosphorylation , fyn , signal transduction , tropomyosin receptor kinase b , neurotrophic factors , cyclin dependent kinase 5 , receptor , proto oncogene tyrosine protein kinase src , protein kinase a , biochemistry , mitogen activated protein kinase kinase , in vitro
D ock3, a new member of the guanine nucleotide exchange factor family, causes cellular morphological changes by activating the small GTP ase R ac1. Overexpression of D ock3 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. Here, we report a novel D ock3‐mediated BDNF pathway for neurite outgrowth. We show that D ock3 forms a complex with Elmo and activated RhoG downstream of BDNF ‐TrkB signaling and induces neurite outgrowth via R ac1 activation in PC 12 cells. We also show the importance of D ock3 phosphorylation in R ac1 activation and show two key events that are necessary for efficient D ock3 phosphorylation: membrane recruitment of D ock3 and interaction of D ock3 with Elmo. These results suggest that D ock3 plays important roles downstream of BDNF signaling in the central nervous system where it stimulates actin polymerization by multiple pathways.