Factors and Functions of ER Morphology

内质网形态的因素和功能

• 批准号: 8628573
• 负责人: Gia Voeltz
• 金额: $ 29.74万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8628573
• 关键词: 3-Dimensional; Actins; Animals; Architecture; Binding; Biogenesis; Cell membrane; Cells; Complement; Complex; Cytoplasm; Cytoskeleton; Data; Endoplasmic Reticulum; Enzymes; Frequencies; Goals; Guanosine Triphosphate Phosphohydrolases; Homo; Inner mitochondrial membrane; Interphase; Interphase Cell; Lead; Link; Lipids; Mammalian Cell; Membrane; Microtubules; Mitochondria; Mitosis; Morphology; Motor; Neuronal Differentiation; Nuclear Envelope; Organelles; Peripheral; Phosphorylation; Play; Polyribosomes; Positioning Attribute; Protein Biosynthesis; Protein Dephosphorylation; Protein Dynamics; Proteins; RNA Splicing; Recruitment Activity; Resolution; Role; Shapes; Site; Structure; Testing; Transmembrane Domain; Variant; Work; constriction; lipid biosynthesis; mutant; paralogous gene; protein folding; public health relevance; tomography

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.

摘要 内质网(ER)具有精细而动态的结构。这 架构由多种汇聚因素和力量决定，包括： 膜形成蛋白，细胞骨架上的动力学，以及丰富的接触部位 发生在内质网和其他细胞器之间。这种相互作用的结果是 ER膜以连续的膜网络分布在细胞质中。 由多个功能域和结构域组成。不同的域可以有多么不同 在连续的膜双层内产生和维护是我们的重点 工作。为了补充这些问题，我们还旨在了解 不同的ER结构域和ER小管动力学的目的。 我以前证明了一类丰富且高度守恒的积分 膜形成蛋白，网状结构，功能稳定的结构 真核生物中的外周内质网小管。然而，对网状病毒是如何形成的知之甚少 膜的形成活动在内质网动态过程中受到调节。我们假设 网状齐聚和/或可逆磷酸化是两种可测试的和 合理的可能的网状功能调节机制。我们也在研究 微管上的动力学如何产生新的内质网小管。为了实现这个目标，我们 最近发现了一个新的因子Rab10，它定位于领先的动态结构域 动态内质网小管边缘8。我们的下一个目标是了解Rab10如何动态 域是形成和调节的。最后，我们最近展示了内质网小管 限制线粒体分裂部位的线粒体17。我们的目标是研究 内质网接触和线粒体收缩的机制和因素 随后在这些位置上进行分裂。