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Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways
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Fuchs, Evelyn, Hass, Alexander K., Spooner, Robert A. , Yoshimura, Shin-ichiro , Lord, Mike and Barr, Francis A. (2007) Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways. Journal of Cell Biology, Vol.177 (No.6). pp. 1133-1143. doi:10.1083/jcb.200612068 ISSN 0021-9525.
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Official URL: http://dx.doi.org/10.1083/jcb.200612068
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.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history > QH301 Biology | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) | ||||
| Library of Congress Subject Headings (LCSH): | Guanosine triphosphate, Eucaryotic cells | ||||
| Journal or Publication Title: | Journal of Cell Biology | ||||
| Publisher: | Rockefeller University Press | ||||
| ISSN: | 0021-9525 | ||||
| Official Date: | 11 June 2007 | ||||
| Dates: |
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| Volume: | Vol.177 | ||||
| Number: | No.6 | ||||
| Page Range: | pp. 1133-1143 | ||||
| DOI: | 10.1083/jcb.200612068 | ||||
| Status: | Peer Reviewed | ||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||
| Funder: | Max-Planck-Gesellschaft zur Förderung der Wissenschaften [Max Planck Society for the Advancement of Science], Deutsche Forschungsgemeinschaft (DFG), National Institutes of Health (U.S.) (NIH) | ||||
| Grant number: | 5 U01AI 65869 (National Institutes of Health) |
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