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Rab10 regulates tubular endosome formation through KIF13A and KIF13B motors

Etoh, Kan, Fukuda, Mitsunori·2019·Journal of Cell Science

Abstract

Recycling endosomes are stations that sort endocytic cargoes to their appropriate destinations. Tubular endosomes have been characterized as a recycling endosomal compartment for clathrin-independent cargoes. However, the molecular mechanism by which tubular endosome formation is regulated is poorly understood. In this study, we identified Rab10 as a novel protein localized at tubular endosomes by using a comprehensive localization screen of EGFP-tagged Rab small GTPases. Knockout of Rab10 completely abolished tubular endosomal structures in HeLaM cells. We also identified kinesin motors KIF13A and KIF13B as novel Rab10-interacting proteins by means of in silico screening. The results of this study demonstrated that both the Rab10-binding homology domain and the motor domain of KIF13A are required for Rab10-positive tubular endosome formation. Our findings provide insight into the mechanism by which the Rab10–KIF13A (or KIF13B) complex regulates tubular endosome formation. This article has an associated First Person interview with the first author of the paper.

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Crossref · 10.1242/jcs.226977

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  • RAB8A and RAB10 colocalize to a perinuclear tubular endocytic recycling compartment.

    “This is consistent with their colocalization to a perinuclear tubular endocytic recycling compartment [37,38,39,40]”
  • RAB10 is widely expressed in peripheral tissues and brain, present in all cell types, and localized to a tubular perinuclear endocytic recycling compartment partially overlapping with RAB8A.

    “It is widely expressed in peripheral tissues as well as in the brain, where it is present in all cell types [36], and localized to a tubular perinuclear endocytic recycling compartment partially overlapping with RAB8A [37,38,39,40].”
  • The study extended the known Retromer regulators to include DENND4A and DENND4C, TBC1D13, and a TBC1D1/TBC1D4 heterodimer, establishing mechanistic links between Retromer and the switching of RAB10 and RAB35.

    “We have now extended these regulators to include DENND4A and DENND4C, TBC1D13, and a TBC1D1/TBC1D4 heterodimer, and in so doing, established mechanistic links between Retromer and the switching of RAB10 and RAB35; two RAB GTPases previously linked to the regulation of endosomal cargo recycling85,88–90,92,96,101,121,122.”
  • Activation of RAB10 is heavily implicated in general endosomal cargo recycling.

    “Activation of RAB10 is heavily implicated in general endosomal cargo recycling85–93”

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Metadata

Authors
Etoh, K., & Fukuda, M.
Affiliations
Graduate School of Life Sciences, Tohoku University Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences , , Aobayama, Aoba-ku, Sendai, Miyagi 980-8578 ,
Venue
Journal of Cell Science
Published
2019-02-19
Volume
132
Issue
5
ISSN
  • 1477-9137
  • 0021-9533
Cited by
106
References
2
Language
en
Funders
  • Ministry of Education, Culture, Sports, Science and Technology (15H04367, 17H05682)
  • Japan Science and Technology Agency (JPMJCR17H4)
  • Japan Society for the Promotion of Science
  • Tohoku University

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