Factors and Functions of ER Morphology

点击翻译按钮获取中文摘要

SUMMARY 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, function to stabilize the structure of 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.