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Type II Transforming Growth Factor-β Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2
Transforming growth factor (TGF)-β family proteins form heteromeric complexes with transmembrane serine/threonine kinases referred to as type I and type II receptors. Ligand binding initiates a signaling cascade that generates a variety of cell type-specific phenotypes. Whereas numerous studies have...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982134/ https://www.ncbi.nlm.nih.gov/pubmed/20881059 http://dx.doi.org/10.1091/mbc.E09-12-1019 |
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author | Penheiter, Sumedha G. Deep Singh, Raman Repellin, Claire E. Wilkes, Mark C. Edens, Maryanne Howe, Philip H. Pagano, Richard E. Leof, Edward B. |
author_facet | Penheiter, Sumedha G. Deep Singh, Raman Repellin, Claire E. Wilkes, Mark C. Edens, Maryanne Howe, Philip H. Pagano, Richard E. Leof, Edward B. |
author_sort | Penheiter, Sumedha G. |
collection | PubMed |
description | Transforming growth factor (TGF)-β family proteins form heteromeric complexes with transmembrane serine/threonine kinases referred to as type I and type II receptors. Ligand binding initiates a signaling cascade that generates a variety of cell type-specific phenotypes. Whereas numerous studies have investigated the regulatory activities controlling TGF-β signaling, there is relatively little information addressing the endocytic and trafficking itinerary of TGF-β receptor subunits. In the current study we have investigated the role of the clathrin-associated sorting protein Disabled-2 (Dab2) in TGF-β receptor endocytosis. Although small interfering RNA-mediated Dab2 knockdown had no affect on the internalization of various clathrin-dependent (i.e., TGF-β, low-density lipoprotein, or transferrin) or -independent (i.e., LacCer) cargo, TGF-β receptor recycling was abrogated. Loss of Dab2 resulted in enlarged early endosomal antigen 1-positive endosomes, reflecting the inability of cargo to traffic from the early endosome to the endosomal recycling compartment and, as documented previously, diminished Smad2 phosphorylation. The results support a model whereby Dab2 acts as a multifunctional adaptor in mesenchymal cells required for TGF-β receptor recycling as well as Smad2 phosphorylation. |
format | Text |
id | pubmed-2982134 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-29821342011-01-30 Type II Transforming Growth Factor-β Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2 Penheiter, Sumedha G. Deep Singh, Raman Repellin, Claire E. Wilkes, Mark C. Edens, Maryanne Howe, Philip H. Pagano, Richard E. Leof, Edward B. Mol Biol Cell Articles Transforming growth factor (TGF)-β family proteins form heteromeric complexes with transmembrane serine/threonine kinases referred to as type I and type II receptors. Ligand binding initiates a signaling cascade that generates a variety of cell type-specific phenotypes. Whereas numerous studies have investigated the regulatory activities controlling TGF-β signaling, there is relatively little information addressing the endocytic and trafficking itinerary of TGF-β receptor subunits. In the current study we have investigated the role of the clathrin-associated sorting protein Disabled-2 (Dab2) in TGF-β receptor endocytosis. Although small interfering RNA-mediated Dab2 knockdown had no affect on the internalization of various clathrin-dependent (i.e., TGF-β, low-density lipoprotein, or transferrin) or -independent (i.e., LacCer) cargo, TGF-β receptor recycling was abrogated. Loss of Dab2 resulted in enlarged early endosomal antigen 1-positive endosomes, reflecting the inability of cargo to traffic from the early endosome to the endosomal recycling compartment and, as documented previously, diminished Smad2 phosphorylation. The results support a model whereby Dab2 acts as a multifunctional adaptor in mesenchymal cells required for TGF-β receptor recycling as well as Smad2 phosphorylation. The American Society for Cell Biology 2010-11-15 /pmc/articles/PMC2982134/ /pubmed/20881059 http://dx.doi.org/10.1091/mbc.E09-12-1019 Text en © 2010 by The American Society for Cell Biology 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). |
spellingShingle | Articles Penheiter, Sumedha G. Deep Singh, Raman Repellin, Claire E. Wilkes, Mark C. Edens, Maryanne Howe, Philip H. Pagano, Richard E. Leof, Edward B. Type II Transforming Growth Factor-β Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2 |
title | Type II Transforming Growth Factor-β Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2 |
title_full | Type II Transforming Growth Factor-β Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2 |
title_fullStr | Type II Transforming Growth Factor-β Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2 |
title_full_unstemmed | Type II Transforming Growth Factor-β Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2 |
title_short | Type II Transforming Growth Factor-β Receptor Recycling Is Dependent upon the Clathrin Adaptor Protein Dab2 |
title_sort | type ii transforming growth factor-β receptor recycling is dependent upon the clathrin adaptor protein dab2 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982134/ https://www.ncbi.nlm.nih.gov/pubmed/20881059 http://dx.doi.org/10.1091/mbc.E09-12-1019 |
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