DOMAIN-SPECIFIC ACTIVATION OF NEURONAL MIGRATION AND NEURITE OUTGROWTH-PROMOTING ACTIVITIES OF LAMININ

The ECM glycoprotein laminin has profound and varied actions on neuron s in vitro. Little is known about how laminin's multiple domains and r eceptor-binding sites interact in determining its overall effects. Her e, it is shown that laminin's ability to promote migration of olfactor y epithelium neuronal cells maps to distal long arm domain E8 and is m ediated by alpha(6) beta(1) integrin. Surprisingly, treatment of lamin in with antibodies against its short arms (domains E1' or P1') uncover ed a new neuronal migration-promoting activity, mediated by a beta(1) integrin other than alpha(6) beta(1). Laminin treated with anti-short arm antibodies also promoted beta(1) integrin-dependent neurite outgro wth from late embryonic retinal neurons, which are normally unresponsi ve to laminin. These ''antibody-induced'' migration and neurite outgro wth activities mapped to laminin's distal long arm, far from the site( s) of antibody binding. Evidence is presented that the induced activit ies are not actually cryptic in laminin, but are suppressed by an acti vity that is located in laminin's P1' domain and that may be lacking i n the laminin homolog merosin.