Regulation of acinar cell function

钙是细胞分泌、蛋白质活化和基因表达的关键调节剂。 因此，解除对细胞内钙处理方式的调节对细胞功能和存活具有可怕的后果。 细胞内钙的储存和特异性释放是由一系列响应外部信号的通道和泵调节的。我的实验室是第一个描述分泌途径钙ATP酶SPCA 2-C的新亚型，它可能参与细胞的功能，通过一个被称为调节胞吐的过程分泌蛋白质。本提案的目的是确定SPCA 2-C在钙调节和细胞功能中的作用。首先，我们研究了SPCA 2-C在胞吐的正常过程中的功能。 使用荧光显微镜和生物化学方法，我们将识别结合SPCA 2-C的蛋白质，以了解它可能影响哪些途径，以帮助调节细胞内的钙浓度和运动。 其次，我们将建立SPCA 2表达增强或去除的细胞和动物模型。 这些模型将通过检查细胞分化、功能和钙处理来表征。具体而言，这些模型将用于确定SPCA 2-C是否参与调节细胞内的钙以影响其功能。这项工作将提供信息，了解钙如何在细胞水平上调节，以及钙如何控制细胞功能，同时还提供了一种新的胞吐过程调节剂的见解。

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.