Molecular mechanisms that regulate polarity and spindle orientation in animals

调节动物极性和纺锤体方向的分子机制

• 批准号: 10397538
• 负责人: Kenneth E Prehoda
• 金额: $ 36.37万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397538
• 关键词: Adult; Animal Organ; Animals; Architecture; Area; Binding; Cell Line; Cell Polarity; Cell membrane; Cell physiology; Cells; Chromosomes; Complex; Development; Disease; Environment; Epithelial Cells; Gastrointestinal tract structure; Goals; Knowledge; Lead; Maintenance; Malignant Neoplasms; Membrane; Mitotic Spindle Apparatus; Mitotic spindle; Molecular; Molecular Motors; Nutrient; Organ; Output; Physiology; Positioning Attribute; Process; Proteins; Rest; Reverse engineering; Set protein; Side; Skin; Specific qualifier value; Structure; Time; Tissues; Translating; Work; animal tissue; case control; daughter cell; enzyme activity; gastrointestinal system; human disease; improved; interest; nerve stem cell; prevent; recruit

Project Abstract Animal cells are asymmetric, often containing different proteins at distinct areas of the membrane. For example, the cells that line our digestive tract are poised to take in nutrients from one side of the cell and deliver them to the rest of the body at the other side. This proposal examines the activity of the Par complex, a set of proteins responsible for creating and maintaining different regions of animal cell membranes. We are also examining how cellular asymmetries are translated into the complex organization seen in animal tissues and organs. One mechanism for creating structure within tissues is to control the placement of the cells that result from a division. This can occur by positioning the mitotic spindle–the apparatus that separates the chromosomes during division–along a particular axis. We are determining how certain areas of the cell membrane recruit molecular motors that generate forces to rotate the spindle into position and construct organized tissues in the process. In general, our work aims to understand how cells process information to specifically target polarity and spindle orientation complexes to the appropriate region of the cell at the right time, activate these complexes once they're localized, and how the activity of these complexes is translated into complex cellular functions. Our goals over the next five years are to identify the molecular interactions that specify polarization of the Par complex in asymmetrically dividing neural stem cells and activate the enzyme activity contained within the complex. In previous work, we determined how the Par complex polarizes its substrates and we are attempting to use this to “reverse engineer” the identification of new polarized proteins. The premise of this project is that knowledge of new polarized factors will help us understand how Par polarity is translated into function, such as the polarized transport found in the epithelial cells in our digestive system. We are also specifically interested in one important polarity output: mitotic spindle orientation. The premise of this project is that animal cells often align their mitotic spindle with the axis of polarity during division. One reason for doing this is that it controls the position of the resulting daughter cells, a feature that is important for the construction and maintenance of complex tissues. Our focus is on a protein that is required to prevent cancer-like over proliferation.

项目摘要 动物细胞是不对称的，通常在细胞的不同区域含有不同的蛋白质。 膜的例如，排列在我们消化道上的细胞随时准备吸收营养 从细胞的一侧传递到身体的另一侧。这项建议 研究了Par复合物的活性，Par复合物是一组负责创造和 维持动物细胞膜的不同区域。我们也在研究细胞 动物组织和器官中的复杂组织结构也体现了这种不对称。 在组织内产生结构的一种机制是控制细胞的位置， 是分裂的结果。这可以通过定位有丝分裂纺锤体（即 在分裂过程中沿着特定的轴将染色体分开。我们正在决定 细胞膜的某些区域募集分子马达，分子马达产生力来旋转细胞膜。 在这个过程中，纺锤体进入位置并构建有组织的组织。总的来说，我们的工作旨在 了解细胞如何处理信息，以专门针对极性和纺锤体方向 在正确的时间将复合物转移到细胞的适当区域，一旦激活这些复合物， 它们是局部的，这些复合物的活性如何转化为复杂的细胞， 功能协调发展的 我们在未来五年的目标是确定分子相互作用， 极化的Par复合物在不对称分裂的神经干细胞，并激活 复合物中所含的酶活性。在以前的工作中，我们确定了Par 复杂的极化其基板，我们正试图利用这一点来“逆向工程”， 鉴定新的极化蛋白。这个项目的前提是， 极化因素将帮助我们理解Par极性如何转化为功能，例如 在我们消化系统的上皮细胞中发现的极化运输。 我们还对一个重要的极性输出特别感兴趣：有丝分裂纺锤体方向。 这个项目的前提是，动物细胞经常将它们的有丝分裂纺锤体与细胞轴对齐。 分裂时的极性这样做的一个原因是，它控制结果 子细胞，这是一个重要的功能，为建设和维护复杂的 组织中我们的重点是防止癌症样过度增殖所需的蛋白质。