The focal adhesion targeting domain of p130Cas confers a mechanosensing function
| Autor: | Bradbury, PM, Turner, K, Mitchell, C, Griffin, KR, Middlemiss, S, Lau, L, Dagg, R, Taran, E, Cooper-White, J, Fabry, B, O'Neill, GM |
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| Rok vydání: | 2017 |
| Předmět: |
Focal Adhesions
Recombinant Fusion Proteins Tetracycline Phosphoproteins Mechanotransduction Cellular Extracellular Matrix Structure-Activity Relationship Protein Transport Crk-Associated Substrate Protein Protein Domains Cell Movement Cell Line Tumor Gene Knockdown Techniques Humans Amino Acid Sequence Phosphorylation Sequence Alignment Developmental Biology Adaptor Proteins Signal Transducing |
| Popis: | © 2017. Published by The Company of Biologists Ltd. Members of the Cas family of focal adhesion proteins contain a highly conserved C-terminal focal adhesion targeting (FAT) domain. To determine the role of the FAT domain in these proteins, we compared wild-type exogenous NEDD9 with a hybrid construct in which the NEDD9 FAT domain had been exchanged for the p130Cas (also known as BCAR1) FAT domain. Fluorescence recovery after photobleaching (FRAP) revealed significantly slowed exchange of the fusion protein at focal adhesions and significantly slower twodimensional migration. No differences were detected in cell stiffness as measured using atomic force microscopy (AFM) and in cell adhesion forces measured with a magnetic tweezer device. Thus, the slowed migration was not due to changes in cell stiffness or adhesion strength. Analysis of cell migration on surfaces of increasing rigidity revealed a striking reduction of cell motility in cells expressing the p130Cas FAT domain. The p130Cas FAT domain induced rigiditydependent phosphorylation of tyrosine residues within NEDD9. This in turn reduced post-translational cleavage of NEDD9, which we show inhibits NEDD9-induced migration. Collectively, our data therefore suggest that the p130Cas FAT domain uniquely confers a mechanosensing function. |
| Databáze: | OpenAIRE |
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