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PMID: 17562788 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways.

The Journal of cell biology ·Vol. 177 ·No. 6 ·2007-06-18 ·Pages 1133-43

Fuchs E, Haas AK, Spooner RA, Yoshimura S, Lord JM, Barr FA

Abstract

Rab family guanosine triphosphatases (GTPases) together with their regulators define specific pathways of membrane traffic within eukaryotic cells. In this study, we have investigated which Rab GTPase-activating proteins (GAPs) can interfere with the trafficking of Shiga toxin from the cell surface to the Golgi apparatus and studied transport of the epidermal growth factor (EGF) from the cell surface to endosomes. This screen identifies 6 (EVI5, RN-tre/USP6NL, TBC1D10A-C, and TBC1D17) of 39 predicted human Rab GAPs as specific regulators of Shiga toxin but not EGF uptake. We show that Rab43 is the target of RN-tre and is required for Shiga toxin uptake. In contrast, RabGAP-5, a Rab5 GAP, was unique among the GAPs tested and reduced the uptake of EGF but not Shiga toxin. These results suggest that Shiga toxin trafficking to the Golgi is a multistep process controlled by several Rab GAPs and their target Rabs and that this process is discrete from ligand-induced EGF receptor trafficking.

MeSH Terms
Endosomes/metabolism Epidermal Growth Factor/metabolism GTPase-Activating Proteins/physiology Golgi Apparatus/metabolism Humans Protein Transport Shiga Toxin/metabolism rab GTP-Binding Proteins/physiology
Chemicals
GTPase-Activating Proteins Epidermal Growth Factor Shiga Toxin rab11 protein rab GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fuchs Evelyn
Department of Cell Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
Haas Alexander K
Spooner Robert A
Yoshimura Shin-ichiro
Lord J Michael
Barr Francis A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200612068
Published
2007-06-18
Epub
2007-00-11
Pages
1133-43
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064371
Subset
IM
Grants
NIAID NIH HHS · U01 AI065869 · United States
PHS HHS · 5 U01A1 65869 · United States
External Links
PubMed source DOI: 10.1083/jcb.200612068 PMC Full Text View journal details
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