Neural Cell Adhesion Molecule Induces Intracellular Signaling via Multiple Mechanisms of Ca2+ Homeostasis

• DOI: 10.1091/mbc.e05-10-0987
• Publication Date: 2006-03-01T20:26:00Z
• Authors: Darya Kiryushko; Irina Korshunova; Vladimir Berezin; Elisabeth Bock
• Keywords: Homeostasis; Cell Signaling

The neural cell adhesion molecule (NCAM) plays a pivotal role in the development of nervous system, promoting neuronal differentiation via homophilic (NCAM-NCAM) as well heterophilic (NCAM-fibroblast growth factor receptor [FGFR]) interactions. NCAM-induced intracellular signaling has been shown to affect and be dependent on cytoplasmic Ca2+ concentration ([Ca2+]i). However, molecular basis this remains unclear. In study, we determined [Ca2+]i regulating mechanisms involved induced by NCAM. To mimic effect NCAM interaction vitro, used peptide derived from binding site NCAM, termed P2, which triggers cascades similar those activated NCAM-NCAM interaction. We found that P2 increased primary hippocampal neurons. This depended two pathways. first pathway was associated with activation FGFR, phospholipase Cgamma, production diacylglycerol, second Src-family kinases. Moreover, NCAM-mediated entry required nonselective cation T-type voltage-gated channels. These channels, together kinases, were also neuritogenesis physiological, Thus, unanticipated homeostasis are contribute differentiation.