Neural cell response to multiple novel sites on laminin-1.

The basement membrane protein laminin-1 is a potent stimulator of neurite outgrowth for a variety of neuronal cell types. Previous studies have identified neurite outgrowth activity in several distinct regions of the laminin-1 molecule. In this study, 545 overlapping 12- to 14-mer synthetic peptides, corresponding to most of the amino acid sequence of the alpha1, beta1, and gamma1 chains of laminin-1, were screened for cell attachment and neurite outgrowth activity using primary cultures of mouse cerebellar granule neurons and two neuronal cell lines. We identified 48 peptides derived from novel regions of the laminin-1 molecule that were positive for neural cell adhesion activity. Only the cerebellar cells were found to have true neurite outgrowth activity with certain of the peptides, whereas some peptides induced short spike-like process with the cell lines. Although 23 of these peptides were active on all 3 cell types screened, 25 others showed cell-type specificity in their activity. These studies show that (1) there are multiple and distinct sites on laminin-1 for cell adhesion and neurite-like outgrowth and (2) that there are neural cell-type-specific active domains. The multiple active sites found explains, in part, the potent activity of laminin-1 on neurite outgrowth.