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Palmitoylation-dependent association with CD63 targets the Ca(2+) sensor synaptotagmin VII to lysosomes
Syt VII is a Ca(2+) sensor that regulates lysosome exocytosis and plasma membrane repair. Because it lacks motifs that mediate lysosomal targeting, it is unclear how Syt VII traffics to these organelles. In this paper, we show that mutations or inhibitors that abolish palmitoylation disrupt Syt VII...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003310/ https://www.ncbi.nlm.nih.gov/pubmed/21041449 http://dx.doi.org/10.1083/jcb.201003021 |
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author | Flannery, Andrew R. Czibener, Cecilia Andrews, Norma W. |
author_facet | Flannery, Andrew R. Czibener, Cecilia Andrews, Norma W. |
author_sort | Flannery, Andrew R. |
collection | PubMed |
description | Syt VII is a Ca(2+) sensor that regulates lysosome exocytosis and plasma membrane repair. Because it lacks motifs that mediate lysosomal targeting, it is unclear how Syt VII traffics to these organelles. In this paper, we show that mutations or inhibitors that abolish palmitoylation disrupt Syt VII targeting to lysosomes, causing its retention in the Golgi complex. In macrophages, Syt VII is translocated simultaneously with the lysosomal tetraspanin CD63 from tubular lysosomes to nascent phagosomes in a Ca(2+)-dependent process that facilitates particle uptake. Mutations in Syt VII palmitoylation sites block trafficking of Syt VII, but not CD63, to lysosomes and phagosomes, whereas tyrosine replacement in the lysosomal targeting motif of CD63 causes both proteins to accumulate on the plasma membrane. Complexes of CD63 and Syt VII are detected only when Syt VII palmitoylation sites are intact. These findings identify palmitoylation-dependent association with the tetraspanin CD63 as the mechanism by which Syt VII is targeted to lysosomes. |
format | Text |
id | pubmed-3003310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-30033102011-05-01 Palmitoylation-dependent association with CD63 targets the Ca(2+) sensor synaptotagmin VII to lysosomes Flannery, Andrew R. Czibener, Cecilia Andrews, Norma W. J Cell Biol Research Articles Syt VII is a Ca(2+) sensor that regulates lysosome exocytosis and plasma membrane repair. Because it lacks motifs that mediate lysosomal targeting, it is unclear how Syt VII traffics to these organelles. In this paper, we show that mutations or inhibitors that abolish palmitoylation disrupt Syt VII targeting to lysosomes, causing its retention in the Golgi complex. In macrophages, Syt VII is translocated simultaneously with the lysosomal tetraspanin CD63 from tubular lysosomes to nascent phagosomes in a Ca(2+)-dependent process that facilitates particle uptake. Mutations in Syt VII palmitoylation sites block trafficking of Syt VII, but not CD63, to lysosomes and phagosomes, whereas tyrosine replacement in the lysosomal targeting motif of CD63 causes both proteins to accumulate on the plasma membrane. Complexes of CD63 and Syt VII are detected only when Syt VII palmitoylation sites are intact. These findings identify palmitoylation-dependent association with the tetraspanin CD63 as the mechanism by which Syt VII is targeted to lysosomes. The Rockefeller University Press 2010-11-01 /pmc/articles/PMC3003310/ /pubmed/21041449 http://dx.doi.org/10.1083/jcb.201003021 Text en © 2010 Flannery et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Flannery, Andrew R. Czibener, Cecilia Andrews, Norma W. Palmitoylation-dependent association with CD63 targets the Ca(2+) sensor synaptotagmin VII to lysosomes |
title | Palmitoylation-dependent association with CD63 targets the Ca(2+) sensor synaptotagmin VII to lysosomes |
title_full | Palmitoylation-dependent association with CD63 targets the Ca(2+) sensor synaptotagmin VII to lysosomes |
title_fullStr | Palmitoylation-dependent association with CD63 targets the Ca(2+) sensor synaptotagmin VII to lysosomes |
title_full_unstemmed | Palmitoylation-dependent association with CD63 targets the Ca(2+) sensor synaptotagmin VII to lysosomes |
title_short | Palmitoylation-dependent association with CD63 targets the Ca(2+) sensor synaptotagmin VII to lysosomes |
title_sort | palmitoylation-dependent association with cd63 targets the ca(2+) sensor synaptotagmin vii to lysosomes |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003310/ https://www.ncbi.nlm.nih.gov/pubmed/21041449 http://dx.doi.org/10.1083/jcb.201003021 |
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