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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...

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Autores principales: Teckchandani, Anjali, Mulkearns, Erin E., Randolph, Timothy W., Toida, Natalie, Cooper, Jonathan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
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.
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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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