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The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis
Endocytic adaptor proteins facilitate cargo recruitment and clathrin-coated pit nucleation. The prototypical clathrin adaptor AP2 mediates cargo recruitment, maturation, and scission of the pit by binding cargo, clathrin, and accessory proteins, including the Eps-homology (EH) domain proteins Eps15...
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/PMC3408417/ https://www.ncbi.nlm.nih.gov/pubmed/22648170 http://dx.doi.org/10.1091/mbc.E11-12-1007 |
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author | Teckchandani, Anjali Mulkearns, Erin E. Randolph, Timothy W. Toida, Natalie Cooper, Jonathan A. |
author_facet | Teckchandani, Anjali Mulkearns, Erin E. Randolph, Timothy W. Toida, Natalie Cooper, Jonathan A. |
author_sort | Teckchandani, Anjali |
collection | PubMed |
description | Endocytic adaptor proteins facilitate cargo recruitment and clathrin-coated pit nucleation. The prototypical clathrin adaptor AP2 mediates cargo recruitment, maturation, and scission of the pit by binding cargo, clathrin, and accessory proteins, including the Eps-homology (EH) domain proteins Eps15 and intersectin. However, clathrin-mediated endocytosis of some cargoes proceeds efficiently in AP2-depleted cells. We found that Dab2, another endocytic adaptor, also binds to Eps15 and intersectin. Depletion of EH domain proteins altered the number and size of clathrin structures and impaired the endocytosis of the Dab2- and AP2-dependent cargoes, integrin β1 and transferrin receptor, respectively. To test the importance of Dab2 binding to EH domain proteins for endocytosis, we mutated the EH domain–binding sites. This mutant localized to clathrin structures with integrin β1, AP2, and reduced amounts of Eps15. Of interest, although integrin β1 endocytosis was impaired, transferrin receptor internalization was unaffected. Surprisingly, whereas clathrin structures contain both Dab2 and AP2, integrin β1 and transferrin localize in separate pits. These data suggest that Dab2-mediated recruitment of EH domain proteins selectively drives the internalization of the Dab2 cargo, integrin β1. We propose that adaptors may need to be bound to their cargo to regulate EH domain proteins and internalize efficiently. |
format | Online Article Text |
id | pubmed-3408417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-34084172012-10-16 The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis Teckchandani, Anjali Mulkearns, Erin E. Randolph, Timothy W. Toida, Natalie Cooper, Jonathan A. Mol Biol Cell Articles Endocytic adaptor proteins facilitate cargo recruitment and clathrin-coated pit nucleation. The prototypical clathrin adaptor AP2 mediates cargo recruitment, maturation, and scission of the pit by binding cargo, clathrin, and accessory proteins, including the Eps-homology (EH) domain proteins Eps15 and intersectin. However, clathrin-mediated endocytosis of some cargoes proceeds efficiently in AP2-depleted cells. We found that Dab2, another endocytic adaptor, also binds to Eps15 and intersectin. Depletion of EH domain proteins altered the number and size of clathrin structures and impaired the endocytosis of the Dab2- and AP2-dependent cargoes, integrin β1 and transferrin receptor, respectively. To test the importance of Dab2 binding to EH domain proteins for endocytosis, we mutated the EH domain–binding sites. This mutant localized to clathrin structures with integrin β1, AP2, and reduced amounts of Eps15. Of interest, although integrin β1 endocytosis was impaired, transferrin receptor internalization was unaffected. Surprisingly, whereas clathrin structures contain both Dab2 and AP2, integrin β1 and transferrin localize in separate pits. These data suggest that Dab2-mediated recruitment of EH domain proteins selectively drives the internalization of the Dab2 cargo, integrin β1. We propose that adaptors may need to be bound to their cargo to regulate EH domain proteins and internalize efficiently. The American Society for Cell Biology 2012-08-01 /pmc/articles/PMC3408417/ /pubmed/22648170 http://dx.doi.org/10.1091/mbc.E11-12-1007 Text en © 2012 Teckchandani 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 BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Teckchandani, Anjali Mulkearns, Erin E. Randolph, Timothy W. Toida, Natalie Cooper, Jonathan A. The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis |
title | The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis |
title_full | The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis |
title_fullStr | The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis |
title_full_unstemmed | The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis |
title_short | The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis |
title_sort | clathrin adaptor dab2 recruits eh domain scaffold proteins to regulate integrin β1 endocytosis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408417/ https://www.ncbi.nlm.nih.gov/pubmed/22648170 http://dx.doi.org/10.1091/mbc.E11-12-1007 |
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