UC Irvine

Neuronal precursors and Immature neurons of the mouse olfactory epithelium (OE) are motile in vho, and can be stimuiated to migrate and are gulded in vito by the ECM protein lanminin (LN) and its homoiogue merosin (MN). LN and MN are also arti-adhesive, i.e. they cause OE neuronal celis to adhere weakly to substrata that would otherwise be strongly adhesive (Cabf and Lander (1991) J. Cel Biol. 115:779). Investigations Into the domains of laminin responsible for its effects on OE celis have revealed the following: The anti-adhesive activity of LN is highly heat stable and maps to the El' fragment of the molecule. Aithough Integrin at1P1 Is a cell-surface receptor krnown to Interact with this reglon of LN, function-bbcking antibodies directed against this integrin do not Inhibit arntiadhesion. The migration-promoting activity of LN Is dstinct from Its anftadhesive activity, and is not the result of adhesion-altering effects of LN. Migration-prmoting acivity is heat-labile, maps to the E8 fragmert of IN, and can be completely blocked by a monoclonal antibody directed against lntegdn subunit a6. Migration promoted by MN, however, Is only partially blocked by this antibody. Surprisingly, aithough LN is not detectably adhesive for OE neuronal cells, some of its domains are. E8 is weakly adhesive, and a recombinant G-domain (rG) Is strongly adhesive. Adhesion to rG was not dependent on aS-containing integrins, nor could it be blocked by a peptide contained In rG that is thought to represent the binding site of integrin a3p1. Adhesion to rG was blocked, however, by low concentrations of hepardn (<20 pgrn) and by antibodies directed against LIN fragment E3 (which Is contained In rG). These data suggest that neuronal adhesion, anti-adhesion and migration can be independently regulated by distinct domains of LN and distinct receptors.