Internalization of the TGF-? type I receptor into caveolin-1 and EEA1 double-positive early endosomes.

ABSTRACT: Endocytosis and intracellular sorting of transforming growth factor-? (TGF-?) receptors play an important regulatory role in TGF-? signaling. Two major endocytic pathways, clathrin- and caveolae-mediated endocytosis, have been reported to independently mediate the internalization of TGF-? receptors. In this study, we demonstrate that the clathrin- and caveolae-mediated endocytic pathways can converge during TGF-? receptor endocytic trafficking. By tracking the intracellular dynamics of fluorescently-labeled TGF-? type I receptor (T?RI), we found that after mediating T?RI internalization, certain clathrin-coated vesicles and caveolar vesicles are fused underneath the plasma membrane, forming a novel type of caveolin-1 and clathrin double-positive vesicles. Under the regulation of Rab5, the fused vesicles are targeted to early endosomes and thus deliver the internalized T?RI to the caveolin-1 and EEA1 double-positive early endosomes (caveolin-1-positive early endosomes). We further showed that the caveolin-1-positive early endosomes are positive for Smad3/SARA, Rab11 and Smad7/Smurf2, and may act as a multifunctional device for TGF-? signaling and TGF-? receptor recycling and degradation. Therefore, these findings uncover a novel scenario of endocytosis, the direct fusion of clathrin-coated and caveolae vesicles during TGF-? receptor endocytic trafficking, which leads to the formation of the multifunctional sorting device, caveolin-1-positive early endosomes, for TGF-? receptors.

SUBMITTER: He K 

PROVIDER: S-EPMC4456627 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature