Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin

The small GTPase Rab7 controls late endocytic transport by the minus end–directed motor protein complex dynein–dynactin, but how it does this is unclear. Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein–related protein 1L (ORP1L) are two effectors of Rab7. We show that GTP-bou...

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Main Authors: Johansson, Marie, Rocha, Nuno, Zwart, Wilbert, Jordens, Ingrid, Janssen, Lennert, Kuijl, Coenraad, Olkkonen, Vesa M., Neefjes, Jacques
Format: Online
Language:English
Published: The Rockefeller University Press 2007
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063981/
id pubmed-2063981
recordtype oai_dc
spelling pubmed-20639812007-11-29 Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin Johansson, Marie Rocha, Nuno Zwart, Wilbert Jordens, Ingrid Janssen, Lennert Kuijl, Coenraad Olkkonen, Vesa M. Neefjes, Jacques Research Articles The small GTPase Rab7 controls late endocytic transport by the minus end–directed motor protein complex dynein–dynactin, but how it does this is unclear. Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein–related protein 1L (ORP1L) are two effectors of Rab7. We show that GTP-bound Rab7 simultaneously binds RILP and ORP1L to form a RILP–Rab7–ORP1L complex. RILP interacts directly with the C-terminal 25-kD region of the dynactin projecting arm p150Glued, which is required for dynein motor recruitment to late endocytic compartments (LEs). Still, p150Glued recruitment by Rab7–RILP does not suffice to induce dynein-driven minus-end transport of LEs. ORP1L, as well as βIII spectrin, which is the general receptor for dynactin on vesicles, are essential for dynein motor activity. Our results illustrate that the assembly of microtubule motors on endosomes involves a cascade of linked events. First, Rab7 recruits two effectors, RILP and ORP1L, to form a tripartite complex. Next, RILP directly binds to the p150Glued dynactin subunit to recruit the dynein motor. Finally, the specific dynein motor receptor Rab7–RILP is transferred by ORP1L to βIII spectrin. Dynein will initiate translocation of late endosomes to microtubule minus ends only after interacting with βIII spectrin, which requires the activities of Rab7–RILP and ORP1L. The Rockefeller University Press 2007-02-12 /pmc/articles/PMC2063981/ /pubmed/17283181 http://dx.doi.org/10.1083/jcb.200606077 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Johansson, Marie
Rocha, Nuno
Zwart, Wilbert
Jordens, Ingrid
Janssen, Lennert
Kuijl, Coenraad
Olkkonen, Vesa M.
Neefjes, Jacques
spellingShingle Johansson, Marie
Rocha, Nuno
Zwart, Wilbert
Jordens, Ingrid
Janssen, Lennert
Kuijl, Coenraad
Olkkonen, Vesa M.
Neefjes, Jacques
Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin
author_facet Johansson, Marie
Rocha, Nuno
Zwart, Wilbert
Jordens, Ingrid
Janssen, Lennert
Kuijl, Coenraad
Olkkonen, Vesa M.
Neefjes, Jacques
author_sort Johansson, Marie
title Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin
title_short Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin
title_full Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin
title_fullStr Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin
title_full_unstemmed Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin
title_sort activation of endosomal dynein motors by stepwise assembly of rab7–rilp–p150glued, orp1l, and the receptor βlll spectrin
description The small GTPase Rab7 controls late endocytic transport by the minus end–directed motor protein complex dynein–dynactin, but how it does this is unclear. Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein–related protein 1L (ORP1L) are two effectors of Rab7. We show that GTP-bound Rab7 simultaneously binds RILP and ORP1L to form a RILP–Rab7–ORP1L complex. RILP interacts directly with the C-terminal 25-kD region of the dynactin projecting arm p150Glued, which is required for dynein motor recruitment to late endocytic compartments (LEs). Still, p150Glued recruitment by Rab7–RILP does not suffice to induce dynein-driven minus-end transport of LEs. ORP1L, as well as βIII spectrin, which is the general receptor for dynactin on vesicles, are essential for dynein motor activity. Our results illustrate that the assembly of microtubule motors on endosomes involves a cascade of linked events. First, Rab7 recruits two effectors, RILP and ORP1L, to form a tripartite complex. Next, RILP directly binds to the p150Glued dynactin subunit to recruit the dynein motor. Finally, the specific dynein motor receptor Rab7–RILP is transferred by ORP1L to βIII spectrin. Dynein will initiate translocation of late endosomes to microtubule minus ends only after interacting with βIII spectrin, which requires the activities of Rab7–RILP and ORP1L.
publisher The Rockefeller University Press
publishDate 2007
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063981/
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