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Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor
The cation-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precursors from the TGN to endosomes. After releasing the hydrolase precursors into the endosomal lumen, the unoccupied receptor returns to the TGN for further rounds of sorting. Here, we show that t...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172094/ https://www.ncbi.nlm.nih.gov/pubmed/15078903 http://dx.doi.org/10.1083/jcb.200312055 |
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author | Arighi, Cecilia N. Hartnell, Lisa M. Aguilar, Ruben C. Haft, Carol R. Bonifacino, Juan S. |
author_facet | Arighi, Cecilia N. Hartnell, Lisa M. Aguilar, Ruben C. Haft, Carol R. Bonifacino, Juan S. |
author_sort | Arighi, Cecilia N. |
collection | PubMed |
description | The cation-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precursors from the TGN to endosomes. After releasing the hydrolase precursors into the endosomal lumen, the unoccupied receptor returns to the TGN for further rounds of sorting. Here, we show that the mammalian retromer complex participates in this retrieval pathway. The hVps35 subunit of retromer interacts with the cytosolic domain of the CI-MPR. This interaction probably occurs in an endosomal compartment, where most of the retromer is localized. In particular, retromer is associated with tubular–vesicular profiles that emanate from early endosomes or from intermediates in the maturation from early to late endosomes. Depletion of retromer by RNA interference increases the lysosomal turnover of the CI-MPR, decreases cellular levels of lysosomal hydrolases, and causes swelling of lysosomes. These observations indicate that retromer prevents the delivery of the CI-MPR to lysosomes, probably by sequestration into endosome-derived tubules from where the receptor returns to the TGN. |
format | Text |
id | pubmed-2172094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21720942008-03-05 Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor Arighi, Cecilia N. Hartnell, Lisa M. Aguilar, Ruben C. Haft, Carol R. Bonifacino, Juan S. J Cell Biol Article The cation-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precursors from the TGN to endosomes. After releasing the hydrolase precursors into the endosomal lumen, the unoccupied receptor returns to the TGN for further rounds of sorting. Here, we show that the mammalian retromer complex participates in this retrieval pathway. The hVps35 subunit of retromer interacts with the cytosolic domain of the CI-MPR. This interaction probably occurs in an endosomal compartment, where most of the retromer is localized. In particular, retromer is associated with tubular–vesicular profiles that emanate from early endosomes or from intermediates in the maturation from early to late endosomes. Depletion of retromer by RNA interference increases the lysosomal turnover of the CI-MPR, decreases cellular levels of lysosomal hydrolases, and causes swelling of lysosomes. These observations indicate that retromer prevents the delivery of the CI-MPR to lysosomes, probably by sequestration into endosome-derived tubules from where the receptor returns to the TGN. The Rockefeller University Press 2004-04-12 /pmc/articles/PMC2172094/ /pubmed/15078903 http://dx.doi.org/10.1083/jcb.200312055 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Arighi, Cecilia N. Hartnell, Lisa M. Aguilar, Ruben C. Haft, Carol R. Bonifacino, Juan S. Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor |
title | Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor |
title_full | Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor |
title_fullStr | Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor |
title_full_unstemmed | Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor |
title_short | Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor |
title_sort | role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172094/ https://www.ncbi.nlm.nih.gov/pubmed/15078903 http://dx.doi.org/10.1083/jcb.200312055 |
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