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EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization

Moren, B. LU ; Shah, C.; Howes, M. T.; Schieber, N. L.; Mcmahon, H. T.; Parton, R. G.; Daumke, O. and Lundmark, R. (2012) In Molecular Biology of the Cell 23(7). p.1316-1329
Abstract
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... (More)
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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
in
Molecular Biology of the Cell
volume
23
issue
7
pages
1316 - 1329
publisher
American Society for Cell Biology
external identifiers
  • scopus:84859396266
ISSN
1059-1524
DOI
10.1091/mbc.E11-09-0787
language
English
LU publication?
no
id
d53723de-4b48-424f-8038-cc0633e96122
alternative location
http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E11-09-0787
date added to LUP
2017-07-06 14:24:46
date last changed
2017-11-12 04:33:29
@article{d53723de-4b48-424f-8038-cc0633e96122,
  abstract     = {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.},
  author       = {Moren, B. and Shah, C. and Howes, M. T. and Schieber, N. L. and Mcmahon, H. T. and Parton, R. G. and Daumke, O. and Lundmark, R.},
  issn         = {1059-1524},
  language     = {eng},
  month        = {04},
  number       = {7},
  pages        = {1316--1329},
  publisher    = {American Society for Cell Biology},
  series       = {Molecular Biology of the Cell},
  title        = {EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization},
  url          = {http://dx.doi.org/10.1091/mbc.E11-09-0787},
  volume       = {23},
  year         = {2012},
}