EAPSI: Characterizing the role of a recently discovered protein in the regulation of calcium signaling and cellular contraction in a model tubular tissue

含有细胞管的组织是人体的重要组成部分，存在于我们的呼吸道和血管中。这些组织对拉伸的适当反应对健康至关重要，而哮喘等疾病是由不受控制的收缩引起的。组织可以通过改变细胞内的钙水平来应对拉伸和调节收缩。微小蠕虫秀丽隐杆线虫的精囊为细胞对拉伸、钙信号和管状组织收缩调节的反应提供了一个极好的模型。精子囊中的许多基因与人类细胞管中的基因相似，荧光传感器允许研究活的、完整的动物的组织。该项目将通过检查最近发现的蛋白质SPV-1在钙信号和细胞收缩调节中的作用，促进我们对细胞管如何响应拉伸的理解。这项工作将在新加坡国立大学与Ronen Zaidel-Bar博士合作进行，他是细胞对机械刺激反应的专家，也是SPV-1的共同发现者。SPV-1含有一个感知膜曲率的F-BAR结构域，一个调节影响组织中肌动球蛋白收缩性的GTPase的RhoGAP结构域，以及一个结合DAG的结构域，DAG是一种由磷脂酶产生的脂质信号分子，是正常组织功能所必需的。这些结构域表明SPV-1可以感知组织拉伸并与细胞调节和收缩网络相互作用，初步证据支持这一点。这项工作将对钙传感器GCaMP和荧光标记的SPV-1进行成像，以研究SPV-1定位如何影响钙信号传导。了解SPV-1在该组织中的作用将促进我们对细胞拉伸反应基础生物学的理解，并可能为治疗药物靶点和组织工程开辟新的途径。该奖项由美国国家科学基金会与新加坡国家研究基金会共同资助。

Tissues containing cellular tubes are vital components of the human body, found in our airways and blood vessels. Proper response of these tissues to stretch is essential to health, and diseases like asthma result from unregulated contraction. Tissues can respond to stretch and regulate contraction by altering calcium levels inside cells. The spermatheca of the microscopic worm C. elegans provides an excellent model for cellular response to stretch, calcium signaling, and regulation of contraction in a tubular tissue. Many genes acting in the spermatheca are similar to the ones in human cellular tubes, and fluorescent sensors allow study of the tissue in a living, intact animal. This project will advance our understanding of how cellular tubes respond to stretch by examining the role of a recently discovered protein, SPV-1, in the regulation of calcium signaling and cellular contraction. This work will be conducted at the National University of Singapore in collaboration with Dr. Ronen Zaidel-Bar, an expert in cell response to mechanical stimuli and co-discoverer of SPV-1. SPV-1 contains an F-BAR domain that senses membrane curvature, a RhoGAP domain that regulates a GTPase known to affect actomyosin contractility in the tissue, and a domain which binds DAG, a lipid signaling molecule generated by a phospholipase required for proper tissue function. These domains suggest SPV-1 can sense tissue stretch and interact with cellular regulatory and contractile networks, and preliminary evidence supports this. This work will image the calcium sensor GCaMP and fluorescently labeled SPV-1 to investigate how SPV-1 localization affects calcium signaling. Understanding SPV-1's role in this tissue will advance our understanding of the fundamental biology of cellular stretch response, and could open new avenues for therapeutic drug targets and tissue engineering. This NSF EAPSI award is funded in collaboration with the National Research Foundation of Singapore.