A NOVEL EXTRACELLULAR DOMAIN VARIANT OF THE HUMAN INTEGRIN ALPHA-7 SUBUNIT GENERATED BY ALTERNATIVE INTRON SPLICING

The integrin alpha 7 beta 1 laminin receptor, which is expressed on re plicating myoblasts, and upregulated during myogenic differentiation, is involved in cell adhesion and communication between muscle cells an d the extracellular matrix. It is a major cell-surface substrate in sk eletal muscle cells for the cell-surface, arginine-specific, ADP-ribos yltransferase. Both the extracellular and cytoplasmic domains of the m ouse alpha 7 subunit undergo alternative splicing during development, generating differentially expressed variants with presumably unique li gand-binding and signalling properties. Here human cDNA clones isolate d from a fetal heart lambda gt10 cDNA library encoded the complete seq uence of the alpha 7 subunit and hybridised to a single major 4.4 kb a lpha 7 subunit transcript abundantly expressed in human skeletal muscl e, moderately expressed in heart, and weakly expressed in most other t issues. One clone out of four contained a novel 225-nucleotide in-fram e deletion corresponding to 75 amino acids in the C-terminal region of the extracellular domain. The variant, whose expression appears to be tissue specific, is created by alternative splicing at sites flanking an intron in the alpha 7 gene. A related mouse form was identified in P19 embryonal carcinoma cells. Deletion of the spliced region, which either contains or is in very close proximity to the major ADP-ribosyl ation site of the alpha 7 subunit, may serve to modulate the effects o f ADP-ribosylation, or alternatively molecular associations, and recep tor-ligand affinity. (C) 1998 Academic Press.