CALCIUM BINDING PROTEINS AND CHEMOSENSORY MECHANISMS

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Vertebrate olfactory signal transduction pathways involve ligand binding activity that activates second messenger systems such adenylate cyclase or phospholipase C activity mediated by G-proteins, resulting in ion movements through cyclic nucleotide gated channels or other cation-selective channels. Calcium, a central component to both pathways, has been implicated to play a key role in olfactory signal generation, adaptation and termination and it has been proposed that a regulatory calcium binding protein is involved. Calcium binding proteins mediate many of the actions of calcium as a second messenger by modulating the activity of target proteins in a calcium dependent manner. A cDNA clone encoding a novel member of the S100 family of calcium binding proteins has been isolated from a catfish (Ictalurus punctatus) olfactory epithelium cDNA library. This protein, named ictacalcin, is particularly interesting as it is present only in chemosensory tissue. Members of this highly conserved, widely distributed superfamily are believed to participate in important cellular regulatory mechanisms such as phosphorylation, exocytosis and cell cycle progression. In light of the role that these proteins play in cell regulation , this study will investigate the potential role of ictacalcin in chemosensory mechanisms by (1) determining the specific cellular localization of ictacalcin in olfactory epithelium (olfactory neurons vs. support cells vs basal cells); (2) identifying its target proteins; and (3) determining its ability to modulate the phosphorylation of proteins in chemosensory tissue. This study will expand knowledge of the role of calcium binding proteins in chemosensory tissue and their possible involvement in chemosensory mechanisms. Elucidating these mechanisms is critical to our understanding of the molecular basis of signal transduction, which offers the promise for novel therapeutic advances in the treatment of metabolic and degenerative diseases associated with aging, oncogenesis, and in response to trauma.