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Rab35 regulates Arf6 activity through centaurin β2/ACAP2 during neurite outgrowth

Kobayashi, Hotaka, Fukuda, Mitsunori·2012·Journal of Cell Science
DOI 10.1242/jcs.098657
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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 cross-talk between Rab and Arf. Although Rab35 and Arf6 were independently reported to regulate same cellular events, including endocytic recycling, phagocytosis, cytokinesis, and neurite outgrowth, the molecular basis that links them remains largely unknown. Here we show evidence that centaurin β2 (also called 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-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 cross-talk between Rab and Arf, i.e., a Rab effector-ArfGAP coupling mechanism, in which ArfGAP is recruited to a specific membrane compartment by its Rab effector function.

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  • RAB35 regulates endosomal exit for cell surface recycling, in part through controlling localised actin dynamics and phosphoinositide metabolism.

    “RAB35 itself regulates endosomal exit for cell surface recycling95–99, in part through controlling localised actin dynamics and phosphoinositide metabolism100,101.”

    From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [99]

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Metadata

Authors
Kobayashi, H., & Fukuda, M.
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2012-01-01
ISSN
  • 1477-9137
  • 0021-9533
DOI
10.1242/jcs.098657
Cited by
110
References
2
Language
en

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