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PMID: 12900393 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Vps27 recruits ESCRT machinery to endosomes during MVB sorting.

The Journal of cell biology ·Vol. 162 ·No. 3 ·2003-08-04 ·Pages 413-23

Katzmann DJ, Stefan CJ, Babst M, Emr SD

Abstract

Down-regulation (degradation) of cell surface proteins within the lysosomal lumen depends on the function of the multivesicular body (MVB) sorting pathway. The function of this pathway requires the class E vacuolar protein sorting (Vps) proteins. Of the class E Vps proteins, both the ESCRT-I complex (composed of the class E proteins Vps23, 28, and 37) and Vps27 (mammalian hepatocyte receptor tyrosine kinase substrate, Hrs) have been shown to interact with ubiquitin, a signal for entry into the MVB pathway. We demonstrate that activation of the MVB sorting reaction is dictated largely through interactions between Vps27 and the endosomally enriched lipid species phosphatidylinositol 3-phosphate via the FYVE domain (Fab1, YGL023, Vps27, and EEA1) of Vps27. ESCRT-I then physically binds to Vps27 on endosomal membranes via a domain within the COOH terminus of Vps27. A peptide sequence in this domain, PTVP, is involved in the function of Vps27 in the MVB pathway, the efficient endosomal recruitment of ESCRT-I, and is related to a motif in HIV-1 Gag protein that is capable of interacting with Tsg101, the mammalian homologue of Vps23. We propose that compartmental specificity for the MVB sorting reaction is the result of interactions of Vps27 with phosphatidylinositol 3-phosphate and ubiquitin. Vps27 subsequently recruits/activates ESCRT-I on endosomes, thereby facilitating sorting of ubiquitinated MVB cargoes.

MeSH Terms
Binding Sites/physiology Carrier Proteins/metabolism Cell Compartmentation/physiology Cells, Cultured Endosomal Sorting Complexes Required for Transport Endosomes/metabolism Eukaryotic Cells/metabolism Intracellular Membranes/metabolism Macromolecular Substances Models, Molecular Peptides/metabolism Phosphatidylinositol 3-Kinases/metabolism Phosphatidylinositol Phosphates/metabolism Protein Structure, Tertiary/physiology Protein Transport/physiology Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins/metabolism Transport Vesicles/metabolism Ubiquitin/metabolism Vacuoles/metabolism Vesicular Transport Proteins
Chemicals
Carrier Proteins Endosomal Sorting Complexes Required for Transport Macromolecular Substances Peptides Phosphatidylinositol Phosphates SRN2 protein, S cerevisiae STP22 protein, S cerevisiae Saccharomyces cerevisiae Proteins Ubiquitin VPS27 protein, S cerevisiae VPS28 protein, S cerevisiae Vesicular Transport Proteins phosphatidylinositol 3-phosphate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Katzmann David J
Department of Cellular and Molecular Medicine, and Howard Hughes Medical Institute, University of California, San Diego School of Medicine, La Jolla, CA 92093-0688, USA.
Stefan Christopher J
Babst Markus
Emr Scott D
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200302136
Published
2003-08-04
Pages
413-23
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172707
Subset
IM
Grants
NCI NIH HHS · CA 58689 · United States
External Links
PubMed source DOI: 10.1083/jcb.200302136 PMC Full Text View journal details
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