Factors and Functions of ER Morphology

描述（由申请人提供）：内质网（ER）具有复杂的动态结构。这种结构是由多种聚合因素和力量决定的，包括：膜成形蛋白，细胞骨架上的动力学，以及ER和其他细胞器之间发生的丰富接触位点。这种相互作用的结果是ER膜作为由多个功能和结构域组成的连续膜网络遍布细胞质。如何在连续的膜双层内产生和维持不同的结构域是我们工作的重点。为了补充这些问题，我们还旨在了解不同ER结构域的功能和ER小管动力学的目的。 我以前证明，一类丰富的和高度保守的完整的膜成形蛋白，网状蛋白，功能稳定的外周内质网小管的结构在真核生物9。然而，很少有人知道如何reticulon膜成形活动的调节过程中ER动态。我们推测，reticulon寡聚化和/或可逆磷酸化是两个可测试的和合理的调节reticulon功能的可能机制。我们也在研究新的内质网小管是如何通过微管上的动力学产生的。为了实现这一目标，我们最近确定了一个新的因素Rab 10，其定位于动态ER tubules 8前沿的动态域。我们的下一个目标是了解Rab 10动态结构域是如何形成和调节的。最后，我们最近发现内质网小管在线粒体分裂的位点限制线粒体17。我们的目的是研究驱动ER接触和线粒体收缩以及随后在这些位置分裂的机制和因素。

DESCRIPTION (provided by applicant): The endoplasmic reticulum (ER) has an elaborate and dynamic architecture. This architecture is determined by multiple converging factors and forces including: membrane shaping proteins, dynamics on the cytoskeleton, and abundant contact sites that occur between the ER and other organelles. The result of this interplay is that the ER membrane is spread throughout the cytoplasm as a continuous membrane network made up of multiple functional and structural domains. How different domains can be generated and maintained within a continuous membrane bilayer is the focus of our work. To complement these questions, we also aim to understand the functions of different ER domains and the purpose of ER tubule dynamics. I previously demonstrated that a class of abundant and highly conserved integral membrane shaping proteins, the reticulons, functions to stabilize the structure of peripheral ER tubules in eukaryotes9. However, little is known about how reticulon membrane shaping activities are regulated during ER dynamics. We hypothesize that reticulon oligomerization and/or reversible phosphorylation are two testable and reasonable possible mechanisms for regulating reticulon function. We are also studying how new ER tubules are generated by dynamics on microtubules. Towards this goal, we recently identified a new factor Rab10 that localizes to a dynamic domain at the leading edge of dynamic ER tubules8. Our next goal is to understand how Rab10 dynamic domains are formed and regulated. Finally, we have recently shown that the ER tubules circumscribe mitochondria at the site of mitochondrial division17. We aim to study the mechanisms and factors that drive ER contact and mitochondrial constriction and subsequent division at these positions.