Integrin and neurocan binding to L1 involves distinct Ig domains

The cell adhesion molecule L1, a 200-220-kDa type I membrane glycoprotein o f the Ig superfamily, mediates many neuronal processes. Originally studied in the nervous system, L1 is expressed by hematopoietic and many epithelial cells, suggesting a more expanded role, L1 supports hemophilic L1-L1 and i ntegrin-mediated cell binding and can also bind with high affinity to the n eural proteoglycan neurocan; however, the binding site is unknown. We have dissected the L1 molecule and investigated the cell binding ability of Ig d omains 1 and 6. We report that RGD sites in domain 6 support alpha 5 beta 1 - or alpha v beta 3-mediated integrin binding and that both RGD sites are e ssential. Cooperation of RGD sites with neighboring domains are necessary f or alpha(5)beta(1). A T cell hybridoma and activated T cells could bind to L1 in the absence of RGDs, This binding was supported by Ig domain 1 and me diated by cell surface-exposed neurocan, Lymphoid and brain-derived neuroca n were structurally similar. We also present evidence that a fusion protein of the Ig 1-like domain of L1 can bind to recombinant neurocan. Our result s support the notion that L1 provides distinct cell binding sites that may serve in cell-cell or cell-matrix interactions.