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EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization
Eps15 homology domain–containing 2 (EHD2) belongs to the EHD-containing protein family of dynamin-related ATPases involved in membrane remodeling in the endosomal system. EHD2 dimers oligomerize into rings on highly curved membranes, resulting in stimulation of the intrinsic ATPase activity. In this...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315815/ https://www.ncbi.nlm.nih.gov/pubmed/22323287 http://dx.doi.org/10.1091/mbc.E11-09-0787 |
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author | Morén, Björn Shah, Claudio Howes, Mark T. Schieber, Nicole L. McMahon, Harvey T. Parton, Robert G. Daumke, Oliver Lundmark, Richard |
author_facet | Morén, Björn Shah, Claudio Howes, Mark T. Schieber, Nicole L. McMahon, Harvey T. Parton, Robert G. Daumke, Oliver Lundmark, Richard |
author_sort | Morén, Björn |
collection | PubMed |
description | Eps15 homology domain–containing 2 (EHD2) belongs to the EHD-containing protein family of dynamin-related ATPases involved in membrane remodeling in the endosomal system. EHD2 dimers oligomerize into rings on highly curved membranes, resulting in stimulation of the intrinsic ATPase activity. In this paper, we report that EHD2 is specifically and stably associated with caveolae at the plasma membrane and not involved in clathrin-mediated endocytosis or endosomal recycling, as previously suggested. EHD2 interacts with pacsin2 and cavin1, and ordered membrane assembly of EHD2 is dependent on cavin1 and caveolar integrity. While the EHD of EHD2 is dispensable for targeting, we identified a loop in the nucleotide-binding domain that, together with ATP binding, is required for caveolar localization. EHD2 was not essential for the formation or shaping of caveolae, but high levels of EHD2 caused distortion and loss of endogenous caveolae. Assembly of EHD2 stabilized and constrained caveolae to the plasma membrane to control turnover, and depletion of EHD2, resulting in endocytic and more dynamic and short-lived caveolae. Thus, following the identification of caveolin and cavins, EHD2 constitutes a third structural component of caveolae involved in controlling the stability and turnover of this organelle. |
format | Online Article Text |
id | pubmed-3315815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33158152012-06-16 EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization Morén, Björn Shah, Claudio Howes, Mark T. Schieber, Nicole L. McMahon, Harvey T. Parton, Robert G. Daumke, Oliver Lundmark, Richard Mol Biol Cell Articles Eps15 homology domain–containing 2 (EHD2) belongs to the EHD-containing protein family of dynamin-related ATPases involved in membrane remodeling in the endosomal system. EHD2 dimers oligomerize into rings on highly curved membranes, resulting in stimulation of the intrinsic ATPase activity. In this paper, we report that EHD2 is specifically and stably associated with caveolae at the plasma membrane and not involved in clathrin-mediated endocytosis or endosomal recycling, as previously suggested. EHD2 interacts with pacsin2 and cavin1, and ordered membrane assembly of EHD2 is dependent on cavin1 and caveolar integrity. While the EHD of EHD2 is dispensable for targeting, we identified a loop in the nucleotide-binding domain that, together with ATP binding, is required for caveolar localization. EHD2 was not essential for the formation or shaping of caveolae, but high levels of EHD2 caused distortion and loss of endogenous caveolae. Assembly of EHD2 stabilized and constrained caveolae to the plasma membrane to control turnover, and depletion of EHD2, resulting in endocytic and more dynamic and short-lived caveolae. Thus, following the identification of caveolin and cavins, EHD2 constitutes a third structural component of caveolae involved in controlling the stability and turnover of this organelle. The American Society for Cell Biology 2012-04-01 /pmc/articles/PMC3315815/ /pubmed/22323287 http://dx.doi.org/10.1091/mbc.E11-09-0787 Text en © 2012 Morén et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Morén, Björn Shah, Claudio Howes, Mark T. Schieber, Nicole L. McMahon, Harvey T. Parton, Robert G. Daumke, Oliver Lundmark, Richard EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization |
title | EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization |
title_full | EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization |
title_fullStr | EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization |
title_full_unstemmed | EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization |
title_short | EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization |
title_sort | ehd2 regulates caveolar dynamics via atp-driven targeting and oligomerization |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315815/ https://www.ncbi.nlm.nih.gov/pubmed/22323287 http://dx.doi.org/10.1091/mbc.E11-09-0787 |
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