NCAM‐induced intracellular signaling revisited

The neural cell adhesion molecule (NCAM) plays a crucial role in neuronal development, synaptic plasticity, and regeneration. NCAM works as ‘‘smart glue’’ that not only mediates cell–cell adhesion but also induces activation of a complex network of intracellular signaling cascades on homophilic or heterophilic binding. Stimulation of NCAM by homophilic interactions induces neuronal differentiation through activation of a number of signaling molecules, including the fibroblast growth factor receptor, non–receptor kinases Fyn and focal adhesion kinase, growth-associated protein-43, the mitogen-activated protein kinase pathway, intracellular Ca 21 , and protein kinases A, C, and G. This review presents and discusses the current knowledge in the area of NCAM signaling with a focus on the events involved in NCAM-mediated neurite outgrowth. V C 2007 Wiley-Liss, Inc.