Exploring Endoplasmic Reticulum-Associated Rab GTPases

探索内质网相关 Rab GTP 酶

• 批准号: RGPIN-2015-04105
• 负责人: Simmen, Thomas
• 金额: $ 2.48万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=589595
• 关键词: Exploring; Endoplasmic; Reticulum; Associated; Rab

The overarching research program of our laboratory is the characterization of mechanisms that lead to the formation of membrane contact sites (MCS), contacts between two organelles. One aspect of our program is the characterization of the mitochondria-associated membrane (MAM), a connection between the endoplasmic reticulum (ER) and mitochondria. Our lab has identified MAM signaling mechanisms, MAM targeting motifs and factors that determine MAM enrichment. For instance, our research has discovered the small GTPase Rab32 as a determinant of MAM enrichment and of the flux of Ca2+ between the ER and mitochondria. Rab32 is a member of the Rab proteins, important regulatory factors for protein secretion, of which about a dozen localize to the ER. Here, these Rabs perform a diversity of functions, some well characterized and resembling the “address tag” function of Rabs of the late secretory pathway, whereas others perform functions that remain poorly understood. What all these ER-associated Rabs have in common is that they determine to varying extents and by various means the localization of ER proteins to membrane domains.

我们实验室的首要研究项目是表征导致膜接触位点（MCS）形成的机制，两个细胞器之间的接触。我们项目的一个方面是线粒体相关膜（MAM）的表征，这是内质网（ER）和线粒体之间的连接。我们的实验室已经确定了MAM信号机制，MAM靶向基序和决定MAM富集的因素。例如，我们的研究发现小GTPase Rab32是MAM富集和内质网与线粒体之间Ca2+通量的决定因素。Rab32是rabb蛋白的一员，是蛋白质分泌的重要调节因子，其中大约有十几个定位于内质网。在这里，这些Rabs具有多种功能，其中一些具有很好的特征，类似于晚期分泌途径Rabs的“地址标签”功能，而其他Rabs的功能仍然知之甚少。所有这些内质网相关的Rabs的共同之处在于它们在不同程度上通过各种方式决定内质网蛋白在膜结构域的定位。