PMC:3649690 / 5020-7785 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3649690","sourcedb":"PMC","sourceid":"3649690","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3649690","text":"3. Cell Adhesion Molecules\nNeural plasticity is a complex and varied process; from neural development, the migration of newly generated neurons, dendritic modifications, and synaptic modulation, many proteins facilitate and contribute to the malleability of neural tissue. Cell adhesion molecules (CAMs) are specialized proteins—typically expressed at the cell surface—which are important in synaptic function, synaptic plasticity, and remodeling of neural circuits [28]. The structure and function of CAMs vary widely within the nervous system, and the categorization and function of each CAM protein involved in neural plasticity are beyond the scope of this review (for a more detailed overview see [28, 29]). This review will instead focus on the potential role of a single CAM, the polysialylated form of neural cell adhesion molecule (PSA-NCAM), in the etiology and treatment of depression. \nThe neural cell adhesion molecule (NCAM) is a member of the immunoglobulin superfamily of cell adhesion molecules and serves to mediate Ca2+-independent cell-cell and cell-extracellular matrix (ECM) interactions [30]. Through homo- and heterophilic interactions, NCAM functions in cell migration, neurite outgrowth and targeting, axonal branching, synaptogenesis, and synaptic plasticity [30–32]. Neural plasticity mediated through the NCAM protein is facilitated through posttranslational modifications, the most important and prevalent of which is glycosylation with polysialic acid (PSA) [33]. Polysialic acid is a linear homopolymer of α2,8-linked sialic acid, which bears a negative charge, acting to abate NCAM-NCAM interactions and therefore interfere with cell adhesion [34]. PSA-NCAM serves to regulate cell-cell and cell-ECM interactions during times of plasticity.\nIn the adult brain PSA-NCAM is expressed on the cell surface of newly generated daughter cells, on neurites during outgrowth and path finding, and at the synapse of mature neurons [30]. The addition of the PSA moiety to NCAM is essential to neural remodelling and synaptic plasticity [10, 35, 36]. Selective cleavage of PSA in the adult brain inhibits activity-induced synaptic plasticity (induction of long-term potentiation (LTP) and long-term depression (LTD)) and alters the normal migration and integration of newly generated neurons within the hippocampus [10, 35], importantly though cleavage of PSA from NCAM does not disrupt normal basal synaptic neurotransmission or alter normal levels of neural proliferation or survival [10, 35]. PSA-NCAM is therefore a particularly interesting protein in that it is one that mediates plasticity at multiple levels, from neural proliferation, integration, differentiation, neuritic outgrowth, synaptogenesis, and modulation of mature 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