The cell adhesion molecule L1: species- and cell-type-dependent multiple binding mechanisms.
The cell adhesion molecule L1 is known to mediate neuronal adhesion, neurite fasciculation, and stimulation of fibroblastin growth factor (FGF)-receptor-dependent neurite outgrowth by homophilic interaction. Recent 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 homophilic binding mechanism of L1 involves multiple domains and has been conserved in chicken neuron-glia cell adhesion molecule (NgCAM) and mammalian L1. The integrin-binding site of L1 contains the tripeptide Arg-Gly-Asp but varies among different species. L1-integrin binding predominates in leucocyte subsets and in 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 leucocyte types. It can be detected in the extracellular matrix and conceivably 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 cerebellum, possibly via modulation of the src signal transduction pathway. The model of L1 binding seems to be governed by the cell, but it does not correlate with known alternative splicing or glycosylation patterns of L1.
Kadmon
G
G
Department of Cellular Immunology 0710, German Cancer Research Centre, Heidelberg, Germany.
Altevogt
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D039841:Leukocyte L1 Antigen Complex; D051379:Mice; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry* / Q000502:physiology*; D017469:Receptors, Fibronectin / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013379:Substrate Specificity
D016023:Integrins; D039841:Leukocyte L1 Antigen Complex; D019006:Neural Cell Adhesion Molecules; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin