Exploring Endoplasmic Reticulum-Associated Rab GTPases

我们实验室的总体研究计划是表征导致膜接触部位(MCS)形成的机制，膜接触部位是两个细胞器之间的接触。我们项目的一个方面是对线粒体相关膜(MAM)的表征，MAM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信号转导机制、MAM靶向基序以及决定MAM浓缩的因素。例如，我们的研究发现，小GTP酶Rab32是MAM丰富和内质网和线粒体之间钙离子流量的决定因素。Rab32是Rab蛋白的一员，Rab蛋白是蛋白质分泌的重要调节因子，其中约有12个定位于内质网。在这里，这些RAB执行不同的功能，其中一些很好地描述并类似于晚期分泌途径中RAB的“地址标签”功能，而另一些执行的功能仍然鲜为人知。所有这些与ER相关的RAB的共同之处在于，它们在不同的程度上通过不同的手段确定ER蛋白在膜结构域的定位。

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.