Rab35 regulates neurite outgrowth and cell shape.
Recent studies have identified Rab35 in the endocytic pathway and as a regulator of cytokinesis; however its molecular mechanisms are currently unknown. Here, we find that Rab35 colocalizes with actin filaments and with Cdc42, Rac1 and RhoA, and that Rab35 can activate Cdc42 both in vivo and in vitro. We find activated Rab35 stimulates neurite outgrowth in PC12 and N1E-115 cells via a Cdc42-dependent pathway and that siRNA knockdown of Rab35 activity abolishes neurite outgrowth in these cell lines. We conclude that one function of Rab35 is to regulate Rho-family GTPases and that this role has consequences for neurite outgrowth.
Chevallier
Julien
J
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Koop
Charles
C
Srivastava
Archana
A
Petrie
Ryan J
RJ
Lamarche-Vane
Nathalie
N
Presley
John F
JF
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D048430:Cell Shape / Q000502:physiology*; D006224:Cricetinae; D048749:Cytokinesis / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D051379:Mice; D016501:Neurites / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
D000199:Actins; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C499134:Rac1 protein, rat; C526380:RhoA protein, mouse; D020764:cdc42 GTP-Binding Protein; D020691:rab GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein