cDNA cloning and chromosomal localization of human alpha(11) integrin - A collagen-binding, I domain-containing, beta(1-)associated integrin alpha-chain present in muscle tissues

We previously identified a novel integrin ru-chain in human fetal muscle ce lls (Gullberg, D,, Veiling, T,, Sjoberg, G., and Sejersen, T, (1995) Dev, D yn. 204, 57-65), We have now isolated the full-length cDNA for this integri n subunit, alpha(11). The open reading frame of the cDNA encodes a precurso r of 1188 amino acids. The predicted mature protein of 1166 amino acids con tains seven conserved FG-GAP repeats, an I domain with a metal ion-dependen t adhesion site motif, a short transmembrane region, and a unique cytoplasm ic domain of 24 amino acids containing the sequence GFFRS, alpha(11), like other I domain integrins, lacks a dibasic cleavage sits for generation of a heavy chain and a light chain, and it contains three potential divalent ca tion binding sites in repeats 5-7, The presence of 22 inserted amino acids in the extracellular stalk portion (amino acids 804-826) distinguishes the alpha(11) integrin sequence from other integrin alpha-chains, Amino acid se quence comparisons reveal the highest identity of 42% with the alpha(10) in tegrin chain. Immunoprecipitation with antibodies to alpha(11) integrin cap tures a 145-kDa protein distinctly larger than the 140-kDa alpha(2) integri n chain when analyzed by SDS-polyacrylamide gel electrophoresis under nonre ducing conditions. Fluorescence in situ hybridization maps the integrin alp ha(11) gene to chromosome 15q23, in the vicinity of an identified locus for Bardet-Biedl syndrome. Based on Northern blotting, integrin alpha(11) mRNA levels are high in the adult human uterus and in the heart and intermediat e in skeletal muscle and some other tissues tested. During in vitro myogeni c differentiation, alpha(11) mRNA and protein are up-regulated. Studies of ligand binding properties show that alpha(11)beta(1) binds collagen type I- Sepharose, and cultured muscle cells localize alpha(11)beta(1) into focal c ontacts on collagen type I. Future studies will reveal the importance of al pha(11)beta(1) for muscle development and integrity in adult muscle and oth er tissues.