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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...

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Autores principales: Penheiter, Sumedha G., Deep Singh, Raman, Repellin, Claire E., Wilkes, Mark C., Edens, Maryanne, Howe, Philip H., Pagano, Richard E., Leof, Edward B.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
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.
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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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