Regulation of acinar cell function

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Calcium is a critical regulator of cell secretion, protein activation, and gene expression. Therefore, de-regulating the way calcium is handled within the cell has dire consequences on cell function and survival. The storage and specific release of calcium within the cell is regulated by a series of channels and pumps that respond to external cues. My laboratory was the first to describe a novel isoform for secretory pathway calcium ATPase, SPCA2-C, which may be involved in the function of cells that secrete proteins through a process known as regulated exocytosis. The objective of this proposal will be to identify the role of SPCA2-C in calcium regulation and cell function. First, we examine how SPCA2-C functions in the normal process of exocytosis. Using fluorescent microscopy and biochemical methodologies, we will identify proteins that bind SPCA2-C to understand which pathways it may affect in helping to regulate calcium concentrations and movement within the cell. Second, we will generate cell and animal models in which the expression of SPCA2 has either been enhanced or removed. These models will be characterized be examining cell differentiation, function and calcium handling. Specifically, these models will be used to determine if the SPCA2-C is involved in regulating calcium within the cell to affect its function. This work will provide information in the understanding of how calcium is regulated at the cellular level and how calcium controls cell function, while also providing insight into a novel regulator of the exocytosis process.