Factors and Functions of ER Morphology

描述（由申请人提供）：内质网（ER）具有复杂而动态的结构。这种结构是由多种聚合因素和力量决定的，包括：膜形成蛋白、细胞骨架上的动力学以及内质网和其他细胞器之间大量的接触位点。这种相互作用的结果是内质网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。如何在一个连续的膜双层中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内质网结构域的功能和内质网小管动力学的目的。我之前证明了一类丰富且高度保守的整体膜形成蛋白，网状蛋白，在真核生物中起稳定外周内质网小管结构的作用。然而，很少知道网状膜形成活动是如何调节内质网动力学。我们假设网状结构寡聚化和/或可逆磷酸化是调节网状结构功能的两种可测试和合理的可能机制。我们也在研究如何通过微管上的动力学产生新的内质网管。为了实现这一目标，我们最近发现了一个新的因子Rab10，它定位于动态内质微管前沿的动态区域8。我们的下一个目标是了解Rab10动态结构域是如何形成和调控的。最后，我们最近发现内质网小管在线粒体分裂的位置包围线粒体17。我们的目的是研究驱动内质网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.