Modulation of α5β1 integrin functions by the phospholipid and cholesterol contents of cell membranes

✍ Scribed by P. Gopalakrishna; S.K. Chaubey; P.S. Manogaran; Gopal Pande

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 694 KB
• Volume: 77
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(20000615)77:4<517::aid-jcb1>3.0.co;2-6

✦ Synopsis

Several modifications of the ␣5␤1 integrin, which alter its intracellular and extracellular interaction with fibronectin and other proteins, have been reported. However, the significance of the lateral mobility of integrin molecules in the plasma membrane, as a regulator of their distribution and function, is poorly understood. We examined this problem by increasing the cholesterol content of plasma membranes, and consequently modifying the fluidity of membrane phospholipids, in rat fibroblasts. Under these conditions, the clustering of ␣5␤1 integrin molecules in focal adhesions, their adhesion to the cell-binding domain of fibronectin, and their association with the cytoskeletal protein talin were significantly enhanced as compared to control cells. However, the activation of MAP-kinase pathways by the association of fibronectin with ␣5␤1 integrin, and its association with integrin-linked kinase (ilk), were suppressed. The treated cells also showed distinct changes in shape, and their actin stress fiber network was more dense and thick as compared to control cells. The changes in fluidity of phospholipids occurred differentially and fluidity of phosphatidyl-ethanolamine increased, while that of phosphatidyl-choline was reduced. Our results suggest that proteins in focal adhesions could be partitioned in specific lipid domains, which regulate specific aspects of ␣5␤1 integrin functions.