Role of Ubiquitylation in Cellular Membrane Transport

Staub, Olivier; Rotin, Daniela

doi:10.1152/physrev.00020.2005

Cited by 191 publications

(178 citation statements)

References 491 publications

(446 reference statements)

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“…Ubiquitination has been shown to play a key role in the internalization and endocytic sorting of membrane receptors (36,37). To test the involvement of the UIMs of epsin 1 in influenza entry, we generated an epsin 1 mutant that lacks the UIM motifs (epsin1⌬UIM).…”

Section: Discussionmentioning

confidence: 99%

Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus

Chen

Zhuang²

2008

Proc. Natl. Acad. Sci. U.S.A.

175

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During clathrin-mediated endocytosis, adaptor proteins recognize specific internalization signals on cargo receptors, either recruiting cargos into clathrin-coated pits (CCPs) or initiating clathrin-coat assembly around the cargo molecules. Here, we identify epsin 1, a clathrin-, ubiquitin-, and phospholipid-interacting protein, as a cargo-specific adaptor for influenza virus entry through the clathrin-mediated pathway. Using live-cell imaging to monitor the entry of individual virus particles, we observed recruitment of epsin 1 to the binding sites of influenza viruses in synchrony with the assembly of CCPs. Epsin 1 knockdown by siRNA significantly inhibited the clathrin-mediated endocytosis of the influenza virus and caused the majority of the virus particles to enter through a clathrin-independent pathway. The same treatment did not affect the entry of several classical ligands for clathrin-mediated endocytosis, including transferrin, LDL, and EGF. Overexpression of the dominant-negative epsin 1 mutant lacking the ubiquitin-interaction motifs nearly completely blocked the clathrin-mediated entry of the influenza virus without affecting transferrin uptake. These results suggest that epsin 1 functions as a cargo-specific adaptor for the clathrin-mediated entry of the influenza virus.

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Section: Discussionmentioning

confidence: 99%

Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus

Chen

Zhuang²

2008

Proc. Natl. Acad. Sci. U.S.A.

175

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“…The fact that a loss-of-function rsp5 mutant is caffeine-sensitive (Dehring et al, 2008) also supports this interpretation. The cellsurface expression of plasma membrane permeases such as those that interact with Sds23 is typically regulated by ubiquitin-dependent vacuolar targeting (Staub and Rotin, 2006). Increased expression of certain transport proteins could cause caffeine resistance by mediating efflux of the drug from cells.…”

Section: Links Between Caffeine Sensitivity and Membrane Protein Dynamentioning

confidence: 99%

Identification of phosphatase 2A‐like Sit4‐mediated signalling and ubiquitin‐dependent protein sorting as modulators of caffeine sensitivity in S. cerevisiae

Hood-DeGrenier¹

2010

Yeast

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Caffeine exerts pleiotropic effects on eukaryotic cells via its ability to act as a lowaffinity adenosine analogue. Here we report that the genes HSE1, RTS3, SDS23 and SDS24 confer caffeine resistance when overexpressed in S. cerevisiae. The Hse1 protein functions in ubiquitin-dependent vacuolar protein sorting, whereas the other proteins are poorly characterized. Bioinformatic analysis of genetic and physical interaction data linked Rts3 and Sds23/24 to the phosphatase 2A-like Sit4 pathway. Combinatorial deletions of the identified suppressor genes conferred varying levels of caffeine hypersensitivity. For hse1 and rts3 mutants, caffeine sensitivity was partially rescued by sorbitol osmostabilization, suggesting possible cell wall integrity defects in these strains. Rapamycin sensitivity experiments linked the caffeine sensitivity of rts3 , but not that of sds23/24 or hse1 strains, to inhibition of the TORC1 kinase complex, a central regulator of cell growth and a known caffeine target. Epistasis experiments support a model in which Rts3 and Sds23/24 act in parallel to negatively regulate Sit4, while Hse1 confers caffeine resistance via a separate pathway. In summary, this study identifies the Sit4 phosphatase pathway and membrane protein dynamics as key modulators of caffeine-mediated inhibition of yeast cell growth and proposes novel functions for Rts3 and Sds23/24.

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“…It is now known that the attachment of a ubiquitin moiety to proteins plays a major role in lysosomal targeting and degradation and is required for the passage of certain cargo molecules into and out of vesicles of the endocytic pathway as well as signaling processes. [11][12][13][14][15][16] Ubiquitin-mediated down-regulation of receptor tyrosine kinases has been observed for a number of different receptors, with the best studied example being EGFR. Importantly, this ubiquitin-dependent sorting to the lysosome is mediated in part by a series of multiprotein complexes termed endosomal sorting complexes required for sorting (ESCRTs).…”

Section: Hepatic Endocytosis: There Is Still a Lot To Learnmentioning

confidence: 99%

A stimulus needed for the study of membrane traffic in hepatocytes

2009

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A major function carried out by the liver is maintenance of the blood chemistry by the continuous secretion of many different serum proteins into the blood sinusoid, transport of solutes and xenobiotics from blood to bile, and filtration of the blood through active internalization of many different receptor-ligand complexes as well as unwanted viral and bacterial pathogens. These primary hepatic secretory and endocytic functions depend on an elaborate cytoskeletal-based vesicle trafficking system that can be modified to meet the specific tasks of moving cargo outward versus inward. Despite the seminal importance of these cell biological processes to the central function of the hepatocyte and general liver physiology, their molecular mechanisms remain poorly defined and remarkably understudied by the hepatology community. Here we provide a short overview of a few important cell biological processes that are performed by hepatocytes and require our attention to better understand liver physiology and disease.

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Role of Ubiquitylation in Cellular Membrane Transport

Cited by 191 publications

References 491 publications

Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus

Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus

Identification of phosphatase 2A‐like Sit4‐mediated signalling and ubiquitin‐dependent protein sorting as modulators of caffeine sensitivity in S. cerevisiae

A stimulus needed for the study of membrane traffic in hepatocytes

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