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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=594419
• 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、蛋白活化和基因表达的重要调节因子。因此，细胞内钙处理方式的失调对细胞功能和存活有可怕的后果。钙在细胞内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来调节的。我的实验室首先描述了一种新的分泌途径钙atp酶的异构体，SPCA2-C，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SPCA2-C在钙调节和细胞功能中的作用。首先，我们研究了SPCA2-C在正常胞吐过程中的作用。使用荧光显微镜和生化方法，我们将识别结合SPCA2-C的蛋白质，以了解它在帮助调节细胞内钙浓度和运动方面可能影响的途径。其次，我们将生成SPCA2表达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从而影响其功能。这项工作将为理解钙如何在细胞水平上被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新调节剂提供见解。