HUMAN SY5Y NEUROBLASTOMA CELL-INTERACTIONS WITH LAMININ ISOFORMS - NEURITE OUTGROWTH ON LAMININ-5 IS MEDIATED BY INTEGRIN ALPHA-3-BETA-1

Laminin (Ln) isoforms may play important roles in neuronal development , particularly axon guidance, but neural receptors mediating interacti ons with Ln are not entirely understood. In this paper, we have compar ed the adhesive and process outgrowth activities of a human neuroblast oma cell line SY5Y on various laminin isoforms. Cell adhesion and proc ess outgrowth were examined on murine Ln-1 (Englebreth-Holm-Swarm sarc oma laminin), human placental Ln-1 (human Ln-1 [p]), human Ln-2 (meros in), human Ln-5 (kalinin/epiligrin/nicein), and human foreskin keratin ocyte extracellular matrix extract (human HFK-ECM). Ln-5 was shown to evoke process outgrowth in amounts comparable to other Ln isoforms. An tibody perturbation experiments showed that adhesion and process outgr owth on murine Ln-1 was primarily mediated by the integrin alpha 1 bet a 1, whereas adhesion and outgrowth on human Ln-5 and human HFK-ECM we re mediated by alpha 3 beta 1. Adhesion to human Ln-1(p) and Ln-2 was not blocked by addition of anti-alpha 1 or anti-alpha 3 antibodies alo ne, but adhesion was partially perturbed when these antibodies were ad ded in combination. Process outgrowth on human Ln-1(p) was blocked whe n either anti-alpha 3 or anti-beta 1 antibodies were added, indicating that alpha 3 beta 1 is the primary integrin heterodimer responsible f or process extension on this substrate. These results demonstrate that Ln-5 and other Ln isoforms support comparable levels of adhesion and process outgrowth, but different integrin heterodimers, alone and in c ombination, are used by SY5Y cells to mediate responses.