Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2920K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rojas, R. Articles by Bonifacino, J. S. Search for Related Content PubMed PubMed Citation Articles by Rojas, R. Articles by Bonifacino, J. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Social Bookmarking                            What's this?

Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7

¹ Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development and ² Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
³ Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands
⁴ Department of Biomolecular Mass Spectrometry, Utrecht University, 3584 CA Utrecht, Netherlands
⁵ Institut Curie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144, Paris 75248, France

Correspondence to P. van der Sluijs: p.vandersluijs{at}umcutrecht.nl; or J.S. Bonifacino: juan{at}helix.nih.gov

The retromer complex mediates retrograde transport of transmembrane cargo from endosomes to the trans-Golgi network (TGN). Mammalian retromer is composed of a sorting nexin (SNX) dimer that binds to phosphatidylinositol 3-phosphate–enriched endosomal membranes and a vacuolar protein sorting (Vps) 26/29/35 trimer that participates in cargo recognition. The mammalian SNX dimer is necessary but not sufficient for recruitment of the Vps26/29/35 trimer to membranes. In this study, we demonstrate that the guanosine triphosphatase Rab7 contributes to this recruitment. The Vps26/29/35 trimer specifically binds to Rab7–guanosine triphosphate (GTP) and localizes to Rab7-containing endosomal domains. Interference with Rab7 function causes dissociation of the Vps26/29/35 trimer but not the SNX dimer from membranes. This blocks retrieval of mannose 6-phosphate receptors to the TGN and impairs cathepsin D sorting. Rab5-GTP does not bind to the Vps26/29/35 trimer, but perturbation of Rab5 function causes dissociation of both the SNX and Vps26/29/35 components from membranes through inhibition of a pathway involving phosphatidylinositol 3-kinase. These findings demonstrate that Rab5 and Rab7 act in concert to regulate retromer recruitment to endosomes.

Abbreviations used in this paper: AP, adapter protein; CI-MPR, cation-independent MPR; GMP-PNP, guanylyl-5'-imidodiphosphate; MPR, mannose 6-phosphate receptor; PI3K, phosphatidylinositol 3-kinase; PI3P, phosphatidylinositol 3-phosphate; SNX, sorting nexin; TfR, transferrin receptor; Vps, vacuolar protein sorting.

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.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Perez-Victoria, F. J., Bonifacino, J. S. (2009). Dual Roles of the Mammalian GARP Complex in Tethering and SNARE Complex Assembly at the trans-Golgi Network. Mol. Cell. Biol. 29: 5251-5263 [Abstract] [Full Text]  
• Seaman, M. N. J., Harbour, M. E., Tattersall, D., Read, E., Bright, N. (2009). Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5. J. Cell Sci. 122: 2371-2382 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents