Regulation of acinar cell function

腺泡细胞功能的调节

• 批准号: 250225-2011
• 负责人: Pin, Christopher
• 金额: $ 2.62万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=547547
• 关键词: Regulation; acinar; cell; function

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.

钙是细胞分泌、蛋白质激活和基因表达的关键调节剂。 因此，取消细胞内钙处理方式的调节会对细胞功能和存活产生可怕的后果。 细胞内钙的储存和特定释放受到一系列响应外部信号的通道和泵的调节。我的实验室是第一个描述分泌途径钙 ATP 酶 SPCA2-C 的新型亚型的实验室，它可能参与通过称为调节胞吐作用的过程分泌蛋白质的细胞的功能。该提案的目的是确定 SPCA2-C 在钙调节和细胞功能中的作用。首先，我们研究 SPCA2-C 在正常的胞吐作用过程中如何发挥作用。 使用荧光显微镜和生化方法，我们将鉴定结合 SPCA2-C 的蛋白质，以了解它可能影响哪些途径，帮助调节细胞内的钙浓度和运动。 其次，我们将生成 SPCA2 表达被增强或去除的细胞和动物模型。 这些模型的特点是检查细胞分化、功能和钙处理。具体来说，这些模型将用于确定 SPCA2-C 是否参与调节细胞内的钙以影响其功能。这项工作将为了解钙如何在细胞水平上受到调节以及钙如何控制细胞功能提供信息，同时还提供对胞吐作用过程的新型调节剂的见解。