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Rab7 palmitoylation is required for efficient endosome-to-TGN trafficking.

Authors
  • Modica, Graziana1
  • Skorobogata, Olga1
  • Sauvageau, Etienne1
  • Vissa, Adriano2, 3, 4
  • Yip, Christopher M3, 4
  • Kim, Peter K2, 3
  • Wurtele, Hugo5, 6
  • Lefrancois, Stephane7, 8
  • 1 Centre INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, Canada. , (Canada)
  • 2 Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. , (Canada)
  • 3 Department of Biochemistry, University of Toronto, Toronto M5G 1X8, Canada. , (Canada)
  • 4 Institute of Biomaterials & Biomedical Engineering and Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada. , (Canada)
  • 5 Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Montréal H1T 2M4, Canada. , (Canada)
  • 6 Département de Médecine, Université de Montréal, Montréal, Québec H3C 3J7, Canada. , (Canada)
  • 7 Centre INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, Canada [email protected] , (Canada)
  • 8 Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 0C7, Canada. , (Canada)
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Aug 01, 2017
Volume
130
Issue
15
Pages
2579–2590
Identifiers
DOI: 10.1242/jcs.199729
PMID: 28600323
Source
Medline
Keywords
License
Unknown

Abstract

Retromer is a multimeric protein complex that mediates endosome-to-trans-Golgi network (TGN) and endosome-to-plasma membrane trafficking of integral membrane proteins. Dysfunction of this complex has been linked to Alzheimer's disease and Parkinson's disease. The recruitment of retromer to endosomes is regulated by Rab7 (also known as RAB7A) to coordinate endosome-to-TGN trafficking of cargo receptor complexes. Rab7 is also required for the degradation of internalized integral membrane proteins, such as the epidermal growth factor receptor (EGFR). We found that Rab7 is palmitoylated and that this modification is not required for membrane anchoring. Palmitoylated Rab7 colocalizes efficiently with and has a higher propensity to interact with retromer than nonpalmitoylatable Rab7. Rescue of Rab7 knockout cells by expressing wild-type Rab7 restores efficient endosome-to-TGN trafficking, while rescue with nonpalmitoylatable Rab7 does not. Interestingly, Rab7 palmitoylation does not appear to be required for the degradation of EGFR or for its interaction with its effector, Rab-interacting lysosomal protein (RILP). Overall, our results indicate that Rab7 palmitoylation is required for the spatiotemporal recruitment of retromer and efficient endosome-to-TGN trafficking of the lysosomal sorting receptors.

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