The TGF-β co-receptor, CD109, promotes internalization and degradation of TGF-β receptors

被引：108

作者：

Bizet, Albane A. ^{[1
]}

Liu, Kai ^{[1
]}

Tran-Khanh, Nicolas ^{[2
]}

Saksena, Anshuman ^{[1
]}

Vorstenbosch, Joshua ^{[1
]}

Finnson, Kenneth W. ^{[1
]}

Buschmann, Michael D. ^{[2
]}

Philip, Anie ^{[1
]}

机构：

[1] McGill Univ, Dept Surg, Div Plast Surg, Montreal, PQ H3G 1A4, Canada

[2] Ecole Polytech, Dept Biomed & Chem Engn, Montreal, PQ H3C 3A7, Canada

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2011年 / 1813卷 / 05期

关键词：

TGF-beta receptor; CD109; Internalization; Degradation; Caveolae; CLATHRIN-MEDIATED ENDOCYTOSIS; INSULIN-RECEPTOR; ACTIVATION SARA; EARLY ENDOSOMES; HUMAN-DISEASE; SMAD ANCHOR; I RECEPTOR; EXPRESSION; CAVEOLAE; DISTINCT;

D O I：

10.1016/j.bbamcr.2011.01.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Transforming growth factor-beta (TGF-beta) is implicated in numerous pathological disorders, including cancer and mediates a broad range of biological responses by signaling through the type I and II TGF-beta receptors. Internalization of these receptors via the clathrin-coated pits pathway facilitates SMAD-mediated signaling, whereas internalization via the caveolae pathway is associated with receptor degradation. Thus, molecules that modulate receptor endocytosis are likely to play a critical role in regulating TGF-beta action. We previously identified CD109, a GPI-anchored protein, as a TGF-beta co-receptor and a negative regulator of TGF-beta signaling. Here, we demonstrate that CD109 associates with caveolin-1, a major component of the caveolae. Moreover, CD109 increases binding of TGF-beta to its receptors and enhances their internalization via the caveolae. In addition, CD109 promotes localization of the TGF-beta receptors into the caveolar compartment in the presence of ligand and facilitates TGF-beta-receptor degradation. Thus, CD109 regulates TGF-beta receptor endocytosis and degradation to inhibit TGF-beta signaling. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：742 / 753

页数：12

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