Contributions of the integrin ?1 tail to cell adhesive forces.

ABSTRACT: Integrin receptors connect the extracellular matrix to the cell cytoskeleton to provide essential forces and signals. To examine the contributions of the ?1 integrin cytoplasmic tail to adhesive forces, we generated cell lines expressing wild-type and tail mutant ?1 integrins in ?1-null fibroblasts. Deletion of ?1 significantly reduced cell spreading, focal adhesion assembly, and adhesive forces, and expression of human ?1 (h?1) integrin in these cells restored adhesive functions. Cells expressing a truncated tail mutant had impaired spreading, fewer and smaller focal adhesions, reduced integrin binding to fibronectin, and lower adhesion strength and traction forces compared to h?1-expressing cells. All these metrics were equivalent to those for ?1-null cells, demonstrating that the ?1 tail is essential to these adhesive functions. Expression of the constitutively-active D759A h?1 mutant restored many of these adhesive functions in ?1-null cells, although with important differences when compared to wild-type ?1. Even though there were no differences in integrin-fibronectin binding and adhesion strength between h?1- and h?1-D759A-expressing cells, h?1-D759A-expressing cells assembled more but smaller adhesions than h?1-expressing cells. Importantly, h?1-D759A-expressing cells generated lower traction forces compared to h?1-expressing cells. These differences between h?1- and h?1-D759A-expressing cells suggest that regulation of integrin activation is important for fine-tuning cell spreading, focal adhesion assembly, and traction force generation.

SUBMITTER: Elloumi-Hannachi I 

PROVIDER: S-EPMC4359961 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature