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

ABSTRACT: Transforming growth factor (TGF)-? 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-? signaling, there is relatively little information addressing the endocytic and trafficking itinerary of TGF-? receptor subunits. In the current study we have investigated the role of the clathrin-associated sorting protein Disabled-2 (Dab2) in TGF-? receptor endocytosis. Although small interfering RNA-mediated Dab2 knockdown had no affect on the internalization of various clathrin-dependent (i.e., TGF-?, low-density lipoprotein, or transferrin) or -independent (i.e., LacCer) cargo, TGF-? 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-? receptor recycling as well as Smad2 phosphorylation.

SUBMITTER: Penheiter SG 

PROVIDER: S-EPMC2982134 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature