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Hsc70 is required for endocytosis and clathrin function in Drosophila
By screening for Drosophila mutants exhibiting aberrant bride of sevenless (Boss) staining patterns on eye imaginal disc epithelia, we have recovered a point mutation in Hsc70-4, the closest homologue to bovine clathrin uncoating ATPase. Although the mutant allele was lethal, analysis of mutant clon...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173062/ https://www.ncbi.nlm.nih.gov/pubmed/12427870 http://dx.doi.org/10.1083/jcb.200205086 |
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author | Chang, Henry C. Newmyer, Sherri L. Hull, Michael J. Ebersold, Melanie Schmid, Sandra L. Mellman, Ira |
author_facet | Chang, Henry C. Newmyer, Sherri L. Hull, Michael J. Ebersold, Melanie Schmid, Sandra L. Mellman, Ira |
author_sort | Chang, Henry C. |
collection | PubMed |
description | By screening for Drosophila mutants exhibiting aberrant bride of sevenless (Boss) staining patterns on eye imaginal disc epithelia, we have recovered a point mutation in Hsc70-4, the closest homologue to bovine clathrin uncoating ATPase. Although the mutant allele was lethal, analysis of mutant clones generated by FLP/FRT recombination demonstrated that the Sevenless-mediated internalization of Boss was blocked in mutant Hsc70-4 eye disc epithelial cells. Endocytosis of other probes was also greatly inhibited in larval Garland cells. Immunostaining and EM analysis of the mutant cells revealed disruptions in the organization of endosomal/lysosomal compartments, including a substantial reduction in the number of clathrin-coated structures in Garland cells. The Hsc70-4 mutation also interacted genetically with a dominant-negative mutant of dynamin, a gene required for the budding of clathrin-coated vesicles (CCVs). Consistent with these phenotypes, recombinant mutant Hsc70 proteins exhibited diminished clathrin uncoating activity in vitro. Together, these data provide genetic support for the long-suspected role of Hsc70 in clathrin-mediated endocytosis, at least in part by inhibiting the uncoating of CCVs. |
format | Text |
id | pubmed-2173062 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21730622008-05-01 Hsc70 is required for endocytosis and clathrin function in Drosophila Chang, Henry C. Newmyer, Sherri L. Hull, Michael J. Ebersold, Melanie Schmid, Sandra L. Mellman, Ira J Cell Biol Article By screening for Drosophila mutants exhibiting aberrant bride of sevenless (Boss) staining patterns on eye imaginal disc epithelia, we have recovered a point mutation in Hsc70-4, the closest homologue to bovine clathrin uncoating ATPase. Although the mutant allele was lethal, analysis of mutant clones generated by FLP/FRT recombination demonstrated that the Sevenless-mediated internalization of Boss was blocked in mutant Hsc70-4 eye disc epithelial cells. Endocytosis of other probes was also greatly inhibited in larval Garland cells. Immunostaining and EM analysis of the mutant cells revealed disruptions in the organization of endosomal/lysosomal compartments, including a substantial reduction in the number of clathrin-coated structures in Garland cells. The Hsc70-4 mutation also interacted genetically with a dominant-negative mutant of dynamin, a gene required for the budding of clathrin-coated vesicles (CCVs). Consistent with these phenotypes, recombinant mutant Hsc70 proteins exhibited diminished clathrin uncoating activity in vitro. Together, these data provide genetic support for the long-suspected role of Hsc70 in clathrin-mediated endocytosis, at least in part by inhibiting the uncoating of CCVs. The Rockefeller University Press 2002-11-11 /pmc/articles/PMC2173062/ /pubmed/12427870 http://dx.doi.org/10.1083/jcb.200205086 Text en Copyright © 2002, 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 Chang, Henry C. Newmyer, Sherri L. Hull, Michael J. Ebersold, Melanie Schmid, Sandra L. Mellman, Ira Hsc70 is required for endocytosis and clathrin function in Drosophila |
title | Hsc70 is required for endocytosis and clathrin function in Drosophila
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title_full | Hsc70 is required for endocytosis and clathrin function in Drosophila
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title_fullStr | Hsc70 is required for endocytosis and clathrin function in Drosophila
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title_full_unstemmed | Hsc70 is required for endocytosis and clathrin function in Drosophila
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title_short | Hsc70 is required for endocytosis and clathrin function in Drosophila
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title_sort | hsc70 is required for endocytosis and clathrin function in drosophila |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173062/ https://www.ncbi.nlm.nih.gov/pubmed/12427870 http://dx.doi.org/10.1083/jcb.200205086 |
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