Details

Autor(en) / Beteiligte

• He, Kangmin
• Yan, Xiaohua
• Li, Nan
• Dang, Song
• Xu, Li
• Zhao, Bing
• Li, Zijian
• Lv, Zhizhen
• Fang, Xiaohong
• Zhang, Youyi
• Chen, Ye-Guang

Titel

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

Ist Teil von

• Cell research, 2015-06, Vol.25 (6), p.738-752

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Endocytosis and intracellular sorting of transforming growth factor-β （TGF-β） receptors play an important reg- ulatory role in TGF-[I signaling. Two major endocytic pathways, clathrin- and caveolae-mediated endocytosis, have been reported to independently mediate the internalization of TGF-β receptors. In this study, we demonstrate that the clathrin- and caveolae-mediated endocytic pathways can converge during TGF-β receptor endocytic trafficking. By tracking the intracellular dynamics of fluoreseently-labeled TGF-β type I receptor （TβRI）, we found that after me- diating TβRI 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 TβRI to the caveolin-1 and EEA1 double-positive early endosomes （caveolin-l-positive early endosomes）. We further showed that the caveolin-l-pos- itive early endosomes are positive for Smad3/SARA, Rabll and Smad7/Smurf2, and may act as a multifunctional device for TGF-β signaling and TGF-β receptor recycling and degradation. Therefore, these findings uncover a novel scenario of endocytosis, the direct fusion of clathrin-coated and caveolae vesicles during TGF-β receptor endocytic trafficking, which leads to the formation of the multifunctional sorting device, caveolin-l-positive early endosomes, for TGF-β receptors.