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Transforming growth factor-beta receptors interact with AP2 by direct binding to beta2 subunit
Diying Yao1, Marcelo Ehrlich, Yoav I Henis
1Department of Biochemistry and Molecular Biology and Thoracic Diseases Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
Molecular Biology of the Cell
|November 14, 2002
Summary
Transforming growth factor-beta (TGF-beta) receptors interact with clathrin-coated pits via beta2-adaptin, not the typical mu2 subunit. This study reveals beta2-adaptin
Area of Science:
- Cell biology
- Molecular and cell biology
- Biochemistry
Background:
- Transforming growth factor-beta (TGF-beta) superfamily members are crucial regulators of biological processes.
- These signals are transduced by type I and type II transmembrane serine/threonine kinase receptors.
- Previous studies suggested TGF-beta receptor internalization involves clathrin-coated pits, but the specific adaptor proteins were unknown.
Purpose of the Study:
- To investigate the involvement of the clathrin-associated adaptor complex AP2 in TGF-beta receptor internalization.
- To identify the specific AP2 subunit that directly binds to TGF-beta receptors.
Main Methods:
- Utilized fluorescence photobleching recovery to assess receptor mobility in live cells.
- Employed yeast two-hybrid screens and in vitro biochemical assays to study receptor-AP2 subunit interactions.
- Manipulated cell conditions (K+ depletion, cytosol acidification, hypertonic medium) to probe coated pit involvement.
Main Results:
- TGF-beta receptor mobility was restricted by interactions with clathrin-coated pits, mediated by receptor cytoplasmic tails.
- Direct binding assays revealed that beta2-adaptin, not mu2, alpha, or sigma2 subunits of AP2, directly interacts with TGF-beta receptor cytoplasmic tails.
- No binding was observed with AP1 complex subunits.
Conclusions:
- Beta2-adaptin directly couples TGF-beta receptors to the AP2 complex and clathrin-coated pits.
- This represents the first in vivo evidence of a transmembrane receptor interacting with beta2-adaptin for coated pit localization.
- The findings elucidate a novel mechanism for TGF-beta receptor trafficking and signaling regulation.
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