A Role of Rab29 in the Integrity of the Trans-Golgi Network and Retrograde Trafficking of Mannose-6-Phosphate Receptor

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Abstract

Rab29 (also referred as Rab7L1) is a novel Rab protein, and is recently demonstrated to regulate phagocytosis and traffic from the Golgi to the lysosome. However, its roles in membrane trafficking have not been investigated extensively. Our results in this study revealed that Rab29 is associated with the trans-Golgi network (TGN), and is essential for maintaining the integrity of the TGN, because inhibition of the activity of Rab29 or depletion of Rab29 resulted in fragmentation of the TGN marked by TGN46. Expression of the dominant negative form Rab29T21N or shRNA-Rab29 also altered the distribution of mannose-6-phosphate receptor (M6PR), and interrupted the retrograde trafficking of M6PR through monitoring the endocytosis of CD8-tagged calcium dependent M6PR (cdM6PR) or calcium independent M6PR (ciM6PR), but without significant effects on the anterograde trafficking of vesicular stomatitis virus G protein (VSV-G). Our results suggest that Rab29 is essential for the integrity of the TGN and participates in the retrograde trafficking of M6PRs.

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Most cited references 25

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Tracing the retrograde route in protein trafficking.

Ludger Johannes, Vincent Popoff (2008)

Retrograde transport, in which proteins and lipids are shuttled between endosomes and biosynthetic/secretory compartments such as the Golgi apparatus, is crucial for a diverse range of cellular functions. Mechanistic studies that explore the molecular machinery involved in this retrograde trafficking route are shedding light on the functions of transport proteins and are providing fresh insights into possible new therapeutic directions.

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Clarifying lysosomal storage diseases.

Kim L Schultz, Luis Tecedor, Michael Chang … (2011)

Lysosomal storage diseases (LSDs) are a class of metabolic disorders caused by mutations in proteins critical for lysosomal function. Such proteins include lysosomal enzymes, lysosomal integral membrane proteins, and proteins involved in the post-translational modification and trafficking of lysosomal proteins. There are many recognized forms of LSDs and, although individually rare, their combined prevalence is estimated to be 1 in 8000 births. Over two-thirds of LSDs involve central nervous system (CNS) dysfunction (progressive cognitive and motor decline) and these symptoms are often the most debilitating. Although the genetic basis for these disorders is clear and the biochemistry of the proteins well understood, the cellular mechanisms by which deficiencies in these proteins disrupt neuronal viability remain ambiguous. In this review, we provide an overview of the widespread cellular perturbations occurring in LSDs, how they might be linked and interventions that may specifically or globally correct those defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

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Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella.

Xiaoyun Liu, Mindy S Spano, Jorge E. Galán (2011)

Unlike broad-host Salmonella serovars, which cause self-limiting disease, Salmonella enterica serovar Typhi can infect only humans causing typhoid fever, a life-threatening systemic disease. The molecular bases for these differences are presently unknown. Here we show that the GTPase Rab29 (Rab7L1) distinguishes the intracellular vacuole of human-adapted and broad-host Salmonella serovars. A screen to identify host factors required for the export of typhoid toxin, which is exclusively encoded by the human-specific Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi (S. Paratyphi) identified Rab29. We found that Rab29 is recruited to the S. Typhi-containing vacuole but not to vacuoles containing broad-host Salmonella. We observed that in cells infected with broad-host Salmonella Rab29 is specifically cleaved by the proteolytic activity of GtgE, a unique type III secretion effector protein that is absent from S. Typhi. An S. Typhi strain engineered to express GtgE and therefore able to cleave Rab29 exhibited increased intracellular replication in human macrophages. These findings indicate significant differences in the intracellular biology of human-adapted and broad-host Salmonella and show how subtle differences in the assortment of effector proteins encoded by highly related pathogens can have a major impact in their biology.

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Author and article information

Contributors

Xiaochen Wang: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 2 May 2014

Volume: 9

Issue: 5

Electronic Location Identifier: e96242

Affiliations

[1 ]School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China

[2 ]Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore, Singapore

National Institute of Biological Sciences, Beijing, China

Author notes

* E-mail: xmuibrwtl@ 123456xmu.edu.cn

Competing Interests: Wanjin Hong is currently the academic editor of PLOS ONE. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Conceived and designed the experiments: TW SW. Performed the experiments: SW ZM XX ZW LS YZ XL. Analyzed the data: TW SW WH. Contributed reagents/materials/analysis tools: ZM XX. Wrote the paper: TW WH SW.

Article

Publisher ID: PONE-D-13-33034

DOI: 10.1371/journal.pone.0096242

PMC ID: 4008501

PubMed ID: 24788816

SO-VID: 0cee83b6-72a9-4727-848c-5e8cdd67859f

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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 7 August 2013

Date accepted : 7 April 2014

Page count

Pages: 12

Funding

This work was supported by National Natural Science Foundation of China (No. 31071176, No. 30971442 and No. 30928011); International S & T Cooperation Program of China (No. 2013DFG32730). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

A Role of Rab29 in the Integrity of the Trans-Golgi Network and Retrograde Trafficking of Mannose-6-Phosphate Receptor

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Most cited references 25

Tracing the retrograde route in protein trafficking.

Clarifying lysosomal storage diseases.

Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella.

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