Factors and Functions of ER Morphology

内质网形态的因素和功能

• 批准号: 8991491
• 负责人: Gia Voeltz
• 金额: $ 29.65万
• 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/8991491
• 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; Health; 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; tomography

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.

描述（由申请人提供）：内质网（ER）具有复杂且动态的结构。这种结构是由多种汇聚因素和力量决定的，包括：膜成形蛋白、细胞骨架的动力学以及内质网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整个细胞质。如何在连续的膜双层内生成和维持不同的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。 我之前证明了一类丰富且高度保守的整体膜成形蛋白（网织蛋白），其功能是稳定真核生物中外周 ER 小管的结构。然而，人们对内质网动力学过程中网织膜成形活动是如何调节的知之甚少。我们假设网状蛋白寡聚化和/或可逆磷酸化是调节网状蛋白功能的两种可测试且合理的可能机制。我们还在研究新的内质网小管是如何通过微管动力学产生的。为了实现这一目标，我们最近发现了一种新因子 Rab10，它定位于动态 ER 小管前缘的动态域8。我们的下一个目标是了解 Rab10 动态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部位限制线粒体17。我们的目标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。