RRC ID 49526
Author Kobayashi H, Fukuda M.
Title Rab35 regulates Arf6 activity through centaurin-β2 (ACAP2) during neurite outgrowth.
Journal J Cell Sci
Abstract Two small GTPases, Rab and Arf, are well-known molecular switches that function in diverse membrane-trafficking routes in a coordinated manner; however, very little is known about the direct crosstalk between Rab and Arf. Although Rab35 and Arf6 were independently reported to regulate the same cellular events, including endocytic recycling, phagocytosis, cytokinesis and neurite outgrowth, the molecular basis that links them remains largely unknown. Here we show that centaurin-β2 (also known as ACAP2) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. We found that Rab35 accumulates at Arf6-positive endosomes in response to nerve growth factor (NGF) stimulation and that centaurin-β2 is recruited to the same compartment in a Rab35-dependent manner. We further showed by knockdown and rescue experiments that after the Rab35-dependent recruitment of centaurin-β2, the Arf6-GAP activity of centaurin-β2 at the Arf6-positive endosomes was indispensable for NGF-induced neurite outgrowth. These findings suggest a novel mode of crosstalk between Rab and Arf: a Rab effector and Arf-GAP coupling mechanism, in which Arf-GAP is recruited to a specific membrane compartment by its Rab effector function.
Volume 125(Pt 9)
Pages 2235-43
Published 2012-5-1
DOI 10.1242/jcs.098657
PII jcs.098657
PMID 22344257
MeSH ADP-Ribosylation Factors / genetics ADP-Ribosylation Factors / metabolism* Animals Endosomes / drug effects Endosomes / metabolism GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism* Gene Expression* / drug effects Gene Knockdown Techniques Nerve Growth Factor / pharmacology Neurites / drug effects Neurites / physiology* PC12 Cells Protein Transport / drug effects Rats Signal Transduction / drug effects Signal Transduction / genetics* rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism*
IF 4.517
Times Cited 75
DNA material pmStr-N1-mouse Arf6 (RDB15387) pEGFP-C1-mouse centaurin-b2-N610A/N691A (RDB15384).