Neural cell response to multiple novel sites on laminin-1

The basement membrane protein laminin-l is a potent stimulator of neurite o utgrowth for a variety of neuronal cell types. Previous studies have identi fied neurite outgrowth activity in several distinct regions of the laminin- l molecule. In this study, 545 overlapping 12- to 14-mer synthetic peptides , corresponding to most of the amino acid sequence of the alpha 1, beta 1, and gamma 1 chains of laminin-l, were screened for cell attachment and neur ite outgrowth activity using primary cultures of mouse cerebellar granule n eurons and two neuronal cell lines. We identified 48 peptides derived from novel regions of the laminin-l molecule that were positive for neural cell adhesion activity. Only the cerebellar cells were found to have true neurit e outgrowth activity with certain of the peptides, whereas some peptides in duced short spike-like process with the cell lines. Although 23 of these pe ptides were active on all 3 cell types screened, 25 others showed cell-type specificity in their activity. These studies show that (1) there are multi ple and distinct sites on laminin-l for cell adhesion and neurite-like outg rowth and (2) that there are neural cell-type-specific active domains. The multiple active sites found explains, in part, the potent activity of lamin in-l on neurite outgrowth. Published 2000 Wiley-Liss, Inc.(dagger)