Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies.
After internalization, ubiquitinated signaling receptors are delivered to early endosomes. There, they are sorted and incorporated into the intralumenal invaginations of nascent multivesicular bodies, which function as transport intermediates to late endosomes. Receptor sorting is achieved by Hrs--a...
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2008
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oai:doaj.org-article:069374da306a43c8b6d9ee4d24b23dcc2021-11-25T05:33:57ZHrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies.1544-91731545-788510.1371/journal.pbio.0060214https://doaj.org/article/069374da306a43c8b6d9ee4d24b23dcc2008-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18767904/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885After internalization, ubiquitinated signaling receptors are delivered to early endosomes. There, they are sorted and incorporated into the intralumenal invaginations of nascent multivesicular bodies, which function as transport intermediates to late endosomes. Receptor sorting is achieved by Hrs--an adaptor--like protein that binds membrane PtdIns3P via a FYVE motif-and then by ESCRT complexes, which presumably also mediate the invagination process. Eventually, intralumenal vesicles are delivered to lysosomes, leading to the notion that EGF receptor sorting into multivesicular bodies mediates lysosomal targeting. Here, we report that Hrs is essential for lysosomal targeting but dispensable for multivesicular body biogenesis and transport to late endosomes. By contrast, we find that the PtdIns3P-binding protein SNX3 is required for multivesicular body formation, but not for EGF receptor degradation. PtdIns3P thus controls the complementary functions of Hrs and SNX3 in sorting and multivesicular body biogenesis.Véronique PonsPierre-Philippe LuyetEtienne MorelLaurence AbramiF Gisou van der GootRobert G PartonJean GruenbergPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 6, Iss 9, p e214 (2008) |
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Biology (General) QH301-705.5 |
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Biology (General) QH301-705.5 Véronique Pons Pierre-Philippe Luyet Etienne Morel Laurence Abrami F Gisou van der Goot Robert G Parton Jean Gruenberg Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. |
description |
After internalization, ubiquitinated signaling receptors are delivered to early endosomes. There, they are sorted and incorporated into the intralumenal invaginations of nascent multivesicular bodies, which function as transport intermediates to late endosomes. Receptor sorting is achieved by Hrs--an adaptor--like protein that binds membrane PtdIns3P via a FYVE motif-and then by ESCRT complexes, which presumably also mediate the invagination process. Eventually, intralumenal vesicles are delivered to lysosomes, leading to the notion that EGF receptor sorting into multivesicular bodies mediates lysosomal targeting. Here, we report that Hrs is essential for lysosomal targeting but dispensable for multivesicular body biogenesis and transport to late endosomes. By contrast, we find that the PtdIns3P-binding protein SNX3 is required for multivesicular body formation, but not for EGF receptor degradation. PtdIns3P thus controls the complementary functions of Hrs and SNX3 in sorting and multivesicular body biogenesis. |
format |
article |
author |
Véronique Pons Pierre-Philippe Luyet Etienne Morel Laurence Abrami F Gisou van der Goot Robert G Parton Jean Gruenberg |
author_facet |
Véronique Pons Pierre-Philippe Luyet Etienne Morel Laurence Abrami F Gisou van der Goot Robert G Parton Jean Gruenberg |
author_sort |
Véronique Pons |
title |
Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. |
title_short |
Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. |
title_full |
Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. |
title_fullStr |
Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. |
title_full_unstemmed |
Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. |
title_sort |
hrs and snx3 functions in sorting and membrane invagination within multivesicular bodies. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2008 |
url |
https://doaj.org/article/069374da306a43c8b6d9ee4d24b23dcc |
work_keys_str_mv |
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1718414558465359872 |