Type II transforming growth factor-β receptor recycling is dependent upon the clathrin adaptor protein Dab2

Sumedha G. Penheiter, Raman Deep Singh, Claire E. Repellin, Mark C. Wilkes, Maryanne Edens, Philip H. Howe, Richard E. Pagano, Edward B. Leof

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4009-4019
Number of pages11
JournalMolecular biology of the cell
Volume21
Issue number22
DOIs
StatePublished - Nov 15 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Penheiter, S. G., Singh, R. D., Repellin, C. E., Wilkes, M. C., Edens, M., Howe, P. H., Pagano, R. E., & Leof, E. B. (2010). Type II transforming growth factor-β receptor recycling is dependent upon the clathrin adaptor protein Dab2. Molecular biology of the cell, 21(22), 4009-4019. https://doi.org/10.1091/mbc.E09-12-1019