| dc.description.abstract | Integrins are cell surface receptors, present in the plasma membrane of cells. The integrin family is composed of 18 α subunits and 8 β subunits, which can combine non-covalently to form 24 different integrin heterodimers. Integrin α11β1 is the major collagen-binding integrin on fibroblasts and is involved in myofibroblast differentiation, wound healing and stromaregulated effects on tumorigenesis. The integrin α11 cytoplasmic tail is suggested to have a role in integrin α11β1 function, but the relative role of individual amino acids in α11 cytoplasmic tail is still unclear. Sequence analysis of α11 cytoplasmic tails revealed that arginine-1174 and lysine-1185 are evolutionary conserved, suggesting that these conserved amino acids contribute to integrin α11 function. To elucidate the potential role of these conserved amino acids in the α11cytoplasmic tail, we mutated the conserved arginine-R1174 and lysine-K1185 to alanines. α11 cDNAs encoding mutant integrin chains, wildtype α11 and cytoplasmic tail deleted α11, were all tagged with EGFP and virally infected and stably expressed in C2C12 mouse myoblasts which lack endogenous collagen receptors. The contribution of the conserved arginine-1174 and lysine-1185 was analyzed in cell adhesion-, focal adhesion formation-, proliferation- and migration assays. Our data demonstrate that the K1185A mutation affected focal adhesion formation, reduced cell proliferation and cell migration. In contrast, the R1174A mutation did not have any significant effect in these assays, except for mediating focal adhesion formation. In summary, our results suggest that conserved lysine-1185 of integrin α11 cytoplasmic tail is essential for α11 integrin function. | |
