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Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes

When internalized receptors and other cargo are destined for lysosomal degradation, they are ubiquitinated and sorted by the ESCRT complexes 0, I, II, and III into multivesicular bodies. Multivesicular bodies are formed when cargo-rich patches of the limiting membrane of endosomes bud inward by an u...

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Detalles Bibliográficos
Autores principales: Wollert, Thomas, Hurley, James H.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851844/
https://www.ncbi.nlm.nih.gov/pubmed/20305637
http://dx.doi.org/10.1038/nature08849
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author Wollert, Thomas
Hurley, James H.
author_facet Wollert, Thomas
Hurley, James H.
author_sort Wollert, Thomas
collection PubMed
description When internalized receptors and other cargo are destined for lysosomal degradation, they are ubiquitinated and sorted by the ESCRT complexes 0, I, II, and III into multivesicular bodies. Multivesicular bodies are formed when cargo-rich patches of the limiting membrane of endosomes bud inward by an unknown mechanism and are then cleaved to yield cargo-bearing intralumenal vesicles. The biogenesis of multivesicular bodies was reconstituted and visualized using giant unilamellar vesicles, fluorescent ESCRT-0, I, II, and III complexes, and a membrane-tethered fluorescent ubiquitin fusion as a model cargo. ESCRT-0 forms domains of clustered cargo but does not deform membranes. ESCRT-I and II in combination deform the membrane into buds, in which cargo is confined. ESCRT-I and II localize to the bud necks, and recruit ESCRT-0-ubiquitin domains to the buds. ESCRT-III subunits localize to the bud neck and efficiently cleave the buds to form intralumenal vesicles. Intralumenal vesicles produced in this reaction contain the model cargo but are devoid of ESCRTs. The observations explain how the ESCRTs direct membrane budding and scission from the cytoplasmic side of the bud without being consumed in the reaction.
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spelling pubmed-28518442010-10-08 Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes Wollert, Thomas Hurley, James H. Nature Article When internalized receptors and other cargo are destined for lysosomal degradation, they are ubiquitinated and sorted by the ESCRT complexes 0, I, II, and III into multivesicular bodies. Multivesicular bodies are formed when cargo-rich patches of the limiting membrane of endosomes bud inward by an unknown mechanism and are then cleaved to yield cargo-bearing intralumenal vesicles. The biogenesis of multivesicular bodies was reconstituted and visualized using giant unilamellar vesicles, fluorescent ESCRT-0, I, II, and III complexes, and a membrane-tethered fluorescent ubiquitin fusion as a model cargo. ESCRT-0 forms domains of clustered cargo but does not deform membranes. ESCRT-I and II in combination deform the membrane into buds, in which cargo is confined. ESCRT-I and II localize to the bud necks, and recruit ESCRT-0-ubiquitin domains to the buds. ESCRT-III subunits localize to the bud neck and efficiently cleave the buds to form intralumenal vesicles. Intralumenal vesicles produced in this reaction contain the model cargo but are devoid of ESCRTs. The observations explain how the ESCRTs direct membrane budding and scission from the cytoplasmic side of the bud without being consumed in the reaction. 2010-03-21 2010-04-08 /pmc/articles/PMC2851844/ /pubmed/20305637 http://dx.doi.org/10.1038/nature08849 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Wollert, Thomas
Hurley, James H.
Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes
title Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes
title_full Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes
title_fullStr Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes
title_full_unstemmed Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes
title_short Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes
title_sort molecular mechanism of multivesicular body biogenesis by escrt complexes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851844/
https://www.ncbi.nlm.nih.gov/pubmed/20305637
http://dx.doi.org/10.1038/nature08849
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