Factors and Functions of ER Morphology

描述(申请人提供)：内质网(ER)有一个精细和动态的结构。这种结构是由多种因素和力量决定的，包括：膜形成蛋白，细胞骨架上的动态，以及内质网与其他细胞器之间发生的丰富的接触部位。这种相互作用的结果是，内质网作为一个由多个功能和结构域组成的连续膜网络分布在细胞质中。如何在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ER结构域的功能和ER小管动力学的目的。我以前证明了一类丰富和高度保守的整合膜形成蛋白，即网状结构，在真核生物中起到稳定外周内质网小管结构的作用。然而，关于网状膜形成活动在内质网动力学过程中是如何调节的，人们知之甚少。我们假设，网状物齐聚和/或可逆的磷酸化是调节网状物功能的两种可检验和合理的可能机制。我们还在研究微管上的动力学是如何产生新的ER管的。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ER管前沿的动态结构域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节的。最后，我们最近发现内质网小管限制了线粒体分裂部位的线粒体17。我们的目标是研究在这些位置上驱动内质网接触和线粒体收缩以及随后分裂的机制和因素。

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.