Discrete spatial organization of TGFβ receptors couples receptor multimerization and signaling to cellular tension
Abstract
Cell surface receptors are central to the cell's ability to generate coordinated responses to the multitude of biochemical and physical cues in the microenvironment. However, the mechanisms by which receptors enable this concerted cellular response remain unclear. To investigate the effect of cellular tension on cell surface receptors, we combined novel high-resolution imaging and single particle tracking with established biochemical assays to examine TGFβ signaling. We find that TGFβ receptors are discretely organized to segregated spatial domains at the cell surface. Integrin-rich focal adhesions organize TβRII around TβRI, limiting the integration of TβRII while sequestering TβRI at these sites. Disruption of cellular tension leads to a collapse of this spatial organization and drives formation of heteromeric TβRI/TβRII complexes and Smad activation. This work details a novel mechanism by which cellular tension regulates TGFβ receptor organization, multimerization, and function, providing new insight into the mechanisms that integrate biochemical and physical cues.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 10, 2015
- Source ID
- 10.7554/elife.09300
Entities
People
- Alma L. Burlingame
- Christopher C. Dufort
- David A. Monteiro
- Joanna P. Rys
- Juan A Oses-Prieto
- Michael W. Davidson
- Michelle A. Baird
- Shreya Chand
- Tamara N Alliston
Organizations
- American Society for Engineering Education
- Florida State University
- Howard Hughes Medical Institute
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Dental and Craniofacial Research
- National Institute of General Medical Sciences
- National Science Foundation
- United States Department of Defense
- University of California
- University of California, San Francisco