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。我的实验室最近发现了一种新型的钙调节剂SPCA 2EXO，它可能参与细胞的功能，这些细胞通过一种称为调节性胞吐的过程分泌蛋白质。该提案的目的是确定SPCA 2EXO在钙调节和细胞功能中的作用。首先，我们将比较SPCA2EXO与先前表征的SPCA2的其他形式的不同之处，以及它如何影响细胞内的钙运动。其次，我们将产生一个小鼠模型，其中我们已经专门删除SPCA 2EXO，并表征对发育和分化的影响。最后，使用细胞培养模型，我们将确定SPCA2EXO的缺失是否影响正常表达SPCA2EXO的细胞进行调节性胞吐的能力。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 has recently identified a novel form of a calcium regulator, SPCA2EXO that 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 SPCA2EXO in calcium regulation and cell function. First, we will compare how SPCA2EXO differs from the other form of SPCA2 that was previously characterized, and how it affects calcium movement within the cell. Secondly, we will generate a mouse model in which we have specifically removed SPCA2EXO, and characterize the effects on development and differentiation. Finally, using a cell culture model, we will determine if loss of SPCA2EXO affects the ability of the cells that normally express SPCA2EXO to undergo regulated exocytosis. 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.