Force-Induced Calpain Cleavage of Talin Is Critical for Growth, Adhesion Development, and Rigidity Sensing

• DOI: 10.1021/acs.nanolett.7b02476
• Publication Date: 2017-10-20T13:52:46Z
• Authors: Mayur Saxena; Rishita Changede; James Hone; Haguy Wolfenson; Michael P. Sheetz
• Keywords: Talin; 0301 basic medicine; Focal Adhesions; Mice; 0303 health sciences; 03 medical and health sciences; Calpain; Cell Movement; Proteolysis; Animals; TRPM Cation Channels; Cell Line; Cell Proliferation

Cell growth depends upon formation of cell-matrix adhesions, but mechanisms detailing the transmission of signals from adhesions to control proliferation are still lacking. Here, we find that the scaffold protein talin undergoes force-induced cleavage in early adhesions to produce the talin rod fragment that is needed for cell cycle progression. Expression of noncleavable talin blocks cell growth, adhesion maturation, proper mechanosensing, and the related property of EGF activation of motility. Further, the expression of talin rod in the presence of noncleavable full-length talin rescues cell growth and other functions. The cleavage of talin is found in early adhesions where there is also rapid turnover of talin that depends upon calpain and TRPM4 activity as well as the generation of force on talin. Thus, we suggest that an important function of talin is its control over cell cycle progression through its cleavage in early adhesions.