The laminin alpha 2-chain short arm mediates cell adhesion through both the alpha 1 beta 1 and alpha 2 beta 1 integrins

Laminin-2, a heterotrimer composed of alpha 2, beta 1, and gamma 1 subunits, is the primary laminin isoform found in muscle and peripheral nerve and is essential for the development and stability of basement membranes in these tissues, Expression of a domain VI-truncated laminin alpha 2-chain results in muscle degeneration and peripheral nerve dysmyelination in the dy(2J) dystrophic mouse, We have expressed amino-terminal domains VI through IVb of the laminin alpha 2-chain, as well as its laminin-1 alpha 1-chain counterpart, to identify candidate cell-interactive functions of this critical region, Using integrin-specific antibodies, recognition sites for the alpha 1 beta 1 and alpha 2 beta 1 integrins were identified in the short arms of both laminin alpha 1- and alpha 2-chain isoforms, Comparisons with a beta-alpha chimeric short arm protein possessing beta 1-chain domain VI further localized these activities to alpha-chain domain VI, In addition, we found that the laminin alpha 2-chain short arm supported neurite outgrowth independent of other laminin-2 subunits, A heparin/heparan sulfate binding activity was also localized to this region of the laminin alpha 2 subunit, These data provide the first evidence that domain VI of the laminin aa-chain mediates interactions with cell surface receptors and suggest that these integrin and heparin binding sites, alone or in concert, may play an important role in muscle and peripheral nerve function.