Cellular signaling by neural cell adhesion molecules of the immunoglobulinsuperfamily

Neural cell adhesion molecules (CAMs) of the immunoglobulin superfamily nuc leate and maintain groups of cells at key sites during early development an d in the adult. In addition to their adhesive properties, binding of CAMs c an affect intracellular signaling. Their ability to influence developmental events, including cell migration, proliferation, and differentiation can t herefore result both from their adhesive as well as their signaling propert ies. This review focuses on the two CAMs for which the most information is known, the neural CAM, N-CAM, and L1. N-CAM was the first CAM 60 be charact erized and, therefore, has been studied extensively. The binding of N-CAM t o cells leads to a number of signaling events, some of which result in chan ges in gene expression. Interest in L1 derives from the fact that mutations in its gene lead to human genetic diseases including mental retardation Mu ch is known about modifications of the L1 cytoplasmic domain and its intera ction with cytoskeletal molecules. The study of CAM signaling mechanisms ha s been assay-dependent rather than molecule-dependent, with particular emph asis on assays of neurite outgrowth and gene expression, an emphasis that i s maintained throughout the review. The signals generated following CAM bin ding that lead to alterations in cell morphology and gene expression have b een linked directly in only a few cases. We also review information on othe r CAMs, giving special consideration to those that are anchored in the memb rane by a phospholipid anchor. These proteins, including a form of N-CAM, a re presumed to be localized in lipid rafts, membrane substructures that inc lude distinctive subsets of cytoplasmic signaling molecules such as members of the src-family of nonreceptor protein tyrosine kinases. In the end, the se studies may reveal that what CAMs do after they bind cells together may have as profound consequences for the cells as the adhesive interactions th emselves. This area will therefore remain a rich ground for future studies. Dev Dyn 2000;218: 260-279. (C) 2000 Wiley-Liss, Inc.