Cellular signaling by neural cell adhesion molecules of the immunoglobulin superfamily
- 1 June 2000
- journal article
- review article
- Published by Wiley in Developmental Dynamics
- Vol. 218 (2), 260-279
- https://doi.org/10.1002/(sici)1097-0177(200006)218:2<260::aid-dvdy3>3.0.co;2-9
Abstract
Neural cell adhesion molecules (CAMs) of the immunoglobulin superfamily nucleate and maintain groups of cells at key sites during early development and in the adult. In addition to their adhesive properties, binding of CAMs can affect intracellular signaling. Their ability to influence developmental events, including cell migration, proliferation, and differentiation can therefore result both from their adhesive as well as their signaling properties. 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 to be characterized and, therefore, has been studied extensively. The binding of N-CAM to cells leads to a number of signaling events, some of which result in changes in gene expression. Interest in L1 derives from the fact that mutations in its gene lead to human genetic diseases including mental retardation. Much is known about modifications of the L1 cytoplasmic domain and its interaction with cytoskeletal molecules. The study of CAM signaling mechanisms has been assay-dependent rather than molecule-dependent, with particular emphasis on assays of neurite outgrowth and gene expression, an emphasis that is maintained throughout the review. The signals generated following CAM binding that lead to alterations in cell morphology and gene expression have been linked directly in only a few cases. We also review information on other CAMs, giving special consideration to those that are anchored in the membrane by a phospholipid anchor. These proteins, including a form of N-CAM, are presumed to be localized in lipid rafts, membrane substructures that include distinctive subsets of cytoplasmic signaling molecules such as members of the src-family of nonreceptor protein tyrosine kinases. In the end, these studies may reveal that what CAMs do after they bind cells together may have as profound consequences for the cells as the adhesive interactions themselves. This area will therefore remain a rich ground for future studies.Keywords
This publication has 95 references indexed in Scilit:
- Tyrosine and serine phosphorylation of the neural cell adhesion molecule L1 is implicated in its oligomannosidic glycan dependent association with NCAM and neurite outgrowthEuropean Journal of Cell Biology, 1998
- Mutational Analysis of the L1 Neuronal Cell Adhesion Molecule Identifies Membrane-Proximal Amino Acids of the Cytoplasmic Domain That Are Required for Cytoskeletal AnchorageMolecular and Cellular Neuroscience, 1997
- Mutations in theDrosophila neuroglian cell adhesion molecule affect motor neuron pathfinding and peripheral nervous system patterningJournal of Neurobiology, 1997
- Mouse and Human SHPS-1: Molecular Cloning of cDNAs and Chromosomal Localization of GenesBiochemical and Biophysical Research Communications, 1997
- Deleted in Colorectal Cancer (DCC) Encodes a Netrin ReceptorCell, 1996
- NCAM Requires a Cytoplasmic Domain to Function as a Neurite Outgrowth-Promoting Neuronal ReceptorMolecular and Cellular Neuroscience, 1995
- The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6Cell, 1994
- The axonal recognition molecule F11 is a multifunctional protein: Specific domains mediate interactions with Ng-CAM and restrictinNeuron, 1993
- Characterization of a heparan sulfate proteoglycan that copurifies with the neural cell adhesion moleculeExperimental Cell Research, 1989
- Neurofascin: A novel chick cell-surface glycoprotein involved in neurite-neurite interactionsCell, 1987