THE CELL-ADHESION MOLECULE L1 - SPECIES-DEPENDENT AND CELL-TYPE-DEPENDENT MULTIPLE BINDING MECHANISMS

The cell adhesion molecule L1 is known to mediate neuronal adhesion, n eurite fasciculation, and stimulation of fibroblastin growth factor (F GF)-receptor-dependent neurite outgrowth by hemophilic interaction. Re cent findings have also revealed heterophilic interactions between L1 and two ''classical'' integrin matrix receptors, murine alpha 5 beta 1 and human alpha V beta 3. The hemophilic binding mechanism of L1 invo lves multiple domains and has been conserved in chicken neuron-glia ce ll adhesion molecule (NgCAM) and mammalian L1. The integrin-binding si te of L1 contains the tripeptide Arg-Gly-Asp but varies among differen t species. L1-integrin binding predominates in leucocyte subsets and i n several tumours. It can mediate homotypic and heterotypic cell-cell adhesion and haptotactic cell movement on substrate-embedded L1. L1 is released in response to cytokines by at least some neuronal and leuco cyte types. It can be detected in the extracellular matrix and conceiv ably contributes to cell and axonal navigation. Antibody perturbation studies indicate that the integrin-binding site of L1 is important for granule cell migration and neurite outgrowth in postnatal murine cere bellum possibly via modulation of the src signal transduction path way . The mode of L1 binding seems to be governed by the cell, but it does not correlate with known alternative splicing or glycosylation patter ns of L1.