Regulation of acinar cell function

钙是细胞分泌、蛋白质激活和基因表达的关键调节因子。因此，去调节细胞内钙的处理方式会对细胞的功能和生存产生可怕的后果。细胞内钙的储存和特定释放受到一系列通道和泵的调节，这些通道和泵对外部信号做出反应。我的实验室是第一个描述分泌途径钙ATPase的新亚型SPCA2-C的实验室，它可能参与细胞通过调节胞吐作用分泌蛋白质的功能。这项建议的目的将是确定SPCA2-C在钙调节和细胞功能中的作用。首先，我们研究SPCA2-C如何在正常的胞吐过程中发挥作用。使用荧光显微镜和生化方法，我们将确定结合SPCA2-C的蛋白质，以了解它可能影响哪些途径来帮助调节细胞内的钙浓度和运动。其次，我们将建立细胞和动物模型，在这些模型中，SPCA2的表达要么增强，要么去除。这些模型将通过检测细胞分化、功能和钙处理来表征。具体地说，这些模型将被用来确定SPCA2-C是否参与调节细胞内的钙以影响其功能。这项工作将为理解钙是如何在细胞水平上调节以及钙如何控制细胞功能提供信息，同时也为胞吐过程的一种新的调节机制提供洞察力。

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.