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Updated: Jun 27, 2026

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Published on: October 27, 2020
Endocytic regulation of TGF-beta signaling
1State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China. ygchen@tsinghua.edu.cn
Abstract:
Transforming growth factor-beta (TGF-beta) signaling is tightly regulated to ensure its proper physiological functions in different cells and tissues. Like other cell surface receptors, TGF-beta receptors are internalized into the cell, and this process plays an important regulatory role in TGF-beta signaling. It is well documented that TGF-beta receptors are endocytosed via clathrin-coated vesicles as TGF-beta endocytosis can be blocked by potassium depletion and the GTPase-deficient dynamin K44A mutant. TGF-beta receptors may also enter cells via cholesterol-rich membrane microdomain lipid rafts/caveolae and are found in caveolin-1-positive vesicles. Although receptor endocytosis is not essential for TGF-beta signaling, clathrin-mediated endocytosis has been shown to promote TGF-beta-induced Smad activation and transcriptional responses. Lipid rafts/caveolae are widely regarded as signaling centers for G protein-coupled receptors and tyrosine kinase receptors, but they are indicated to facilitate the degradation of TGF-beta receptors and therefore turnoff of TGF-beta signaling. This review summarizes current understanding of TGF-beta receptor endocytosis, the possible mechanisms underlying this process, and the role of endocytosis in modulation of TGF-beta signaling.
Insights
Transforming growth factor-beta (TGF-beta) receptor endocytosis is a key regulator of cell signaling. This review explores how clathrin-mediated and lipid raft pathways influence TGF-beta receptor internalization and signaling outcomes.
Area of Science:
- Cell biology
- Molecular signaling
- Receptor trafficking
Background:
- Transforming growth factor-beta (TGF-beta) signaling is crucial for physiological processes.
- TGF-beta receptor internalization is a significant regulatory mechanism.
- Understanding receptor endocytosis is vital for comprehending TGF-beta pathway modulation.
Purpose of the Study:
- To review the current knowledge on TGF-beta receptor endocytosis.
- To elucidate the mechanisms involved in TGF-beta receptor internalization.
- To examine the role of endocytosis in modulating TGF-beta signaling.
Main Methods:
- Literature review of studies on TGF-beta receptor endocytosis.
- Analysis of mechanisms including clathrin-coated vesicles and lipid rafts.
- Investigation of the impact of endocytosis on Smad activation and transcriptional responses.
Main Results:
- TGF-beta receptors are internalized via clathrin-coated vesicles and lipid rafts/caveolae.
- Clathrin-mediated endocytosis promotes TGF-beta-induced Smad activation.
- Lipid rafts may facilitate TGF-beta receptor degradation, terminating signaling.
Conclusions:
- Receptor endocytosis is a critical regulator of TGF-beta signaling.
- Distinct endocytic pathways differentially impact TGF-beta signaling outcomes.
- Further research into these pathways can reveal therapeutic targets.
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