The neural cell adhesion molecule (NCAM), originally described by Jorgensen and Bock in 1974 as a synaptic membrane glycoprotein termed D21, was the first vertebrate molecule to be identified and characterized by the Edelman group as a cell adhesion molecule2. This glycoprotein is widely expressed in the central and peripheral nervous systems, and decades of intensive research have disclosed a great deal of information on structure, interaction partners, signaling pathways, and functions of NCAM. Interestingly, in the mammalian brain, NCAM is a unique carrier of the unusual polyanionic carbohydrate, polysialic acid (PSA). Functions of NCAM appear to depend on PSA, providing probably one of the most impressive examples in neurobiology of how glycosylation may modify the activity of a protein. In this chapter, I discuss emerging multiple mechanisms by which NCAM and associated PSA affect synaptogenesis, transmitter release, and synaptic plasticity.
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