PMID- 22734669 OWN - NLM STAT- MEDLINE DCOM- 20121206 LR - 20201209 IS - 1365-2443 (Electronic) IS - 1356-9597 (Linking) VI - 17 IP - 8 DP - 2012 Aug TI - Dock3 regulates BDNF-TrkB signaling for neurite outgrowth by forming a ternary complex with Elmo and RhoG. PG - 688-97 LID - 10.1111/j.1365-2443.2012.01616.x [doi] AB - 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. Here, we report a novel Dock3-mediated BDNF pathway for neurite outgrowth. We show that Dock3 forms a complex with Elmo and activated RhoG downstream of BDNF-TrkB signaling and induces neurite outgrowth via Rac1 activation in PC12 cells. We also show the importance of Dock3 phosphorylation in Rac1 activation and show 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. CI - (c) 2012 The Authors Journal compilation (c) 2012 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd. FAU - Namekata, Kazuhiko AU - Namekata K AD - Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan. FAU - Watanabe, Hayaki AU - Watanabe H FAU - Guo, Xiaoli AU - Guo X FAU - Kittaka, Daiji AU - Kittaka D FAU - Kawamura, Kazuto AU - Kawamura K FAU - Kimura, Atsuko AU - Kimura A FAU - Harada, Chikako AU - Harada C FAU - Harada, Takayuki AU - Harada T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120627 PL - England TA - Genes Cells JT - Genes to cells : devoted to molecular & cellular mechanisms JID - 9607379 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carrier Proteins) RN - 0 (Dock3 protein, mouse) RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuropeptides) RN - 0 (Rac1 protein, mouse) RN - 0 (Rhog protein, mouse) RN - 0 (Ternary Complex Factors) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.6.1.- (GTP Phosphohydrolases) RN - EC 3.6.5.2 (rac GTP-Binding Proteins) RN - EC 3.6.5.2 (rac1 GTP-Binding Protein) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) SB - IM MH - Adaptor Proteins, Signal Transducing/genetics/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - COS Cells MH - Carrier Proteins/genetics/*metabolism MH - Cell Membrane/genetics/metabolism MH - Chlorocebus aethiops MH - Enzyme Activation MH - GTP Phosphohydrolases/genetics/metabolism MH - Guanine Nucleotide Exchange Factors MH - Mice MH - Mice, Inbred C57BL MH - Nerve Tissue Proteins/genetics/*metabolism MH - Neurites/drug effects/*metabolism/physiology MH - Neuropeptides/genetics/metabolism MH - PC12 Cells MH - Phosphorylation MH - Protein Interaction Mapping MH - Protein Transport MH - Rats MH - Receptor, trkB/genetics/*metabolism MH - *Signal Transduction MH - Ternary Complex Factors/genetics/*metabolism MH - Transfection MH - rac GTP-Binding Proteins/genetics/metabolism MH - rac1 GTP-Binding Protein MH - rho GTP-Binding Proteins EDAT- 2012/06/28 06:00 MHDA- 2012/12/10 06:00 CRDT- 2012/06/28 06:00 PHST- 2011/07/13 00:00 [received] PHST- 2012/04/25 00:00 [accepted] PHST- 2012/06/28 06:00 [entrez] PHST- 2012/06/28 06:00 [pubmed] PHST- 2012/12/10 06:00 [medline] AID - 10.1111/j.1365-2443.2012.01616.x [doi] PST - ppublish SO - Genes Cells. 2012 Aug;17(8):688-97. doi: 10.1111/j.1365-2443.2012.01616.x. Epub 2012 Jun 27.