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.

概括 内质网（ER）具有精致且动态的结构。这 架构由多个融合因素和力量决定： 膜形成蛋白质，细胞骨架上的动力学和丰富的接触位点 这发生在ER和其他细胞器之间。这个相互作用的结果是 ER膜作为连续膜网络遍布整个细胞质 由多个功能和结构域组成。如何不同的域 在连续的膜双层中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域和ER小管动力学的目的。 我以前证明了一类丰富且高度保守的积分 膜形成蛋白质，网状元素的功能，可稳定稳定的结构 真核生物中的外围ER小管9。但是，关于片段的知识知之甚少 在ER动力学期间，调节​​膜形状活性。我们假设这一点 网状寡聚和/或可逆磷酸化是两个可检验的，并且 调节网状功能的合理可能机制。我们也在学习 如何通过微管上的动力学生成新的ER小管。达到这个目标，我们 最近确定了一种新的因子RAB10，该因子本地化在领先的动态域 动态ER小管的边缘8。我们的下一个目标是了解Rab10如何动态 域形成和调节。最后，我们最近显示了ER小管 在线粒体司的位置限制线粒体17。我们旨在研究 驱动ER接触和线粒体收缩的机制和因素 随后在这些职位上的划分。