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: 10152623
• 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/10152623
• 关键词: Adult; Animal Organ; Animals; Architecture; Area; Binding; Cell Line; Cell Polarity; Cell membrane; Cell physiology; Cells; Chromosomes; Complex; Development; Disease; Engineering; 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; 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，通常在不同区域含有不同的蛋白质 膜。例如，消化道内的细胞准备好吸收营养 从细胞的一侧将它们输送到另一侧的身体其他部位。这个提议 检查 Par 复合物的活性，Par 复合物是一组负责产生和 维持动物细胞膜的不同区域。我们也在研究细胞如何 不对称性转化为动物组织和器官中可见的复杂组织。 在组织内创建结构的一种机制是控制细胞的位置 分裂的结果。这可以通过定位有丝分裂纺锤体来实现——该装置 在分裂过程中沿着特定的轴分离染色体。我们正在确定如何 细胞膜的某些区域招募分子马达，产生旋转细胞的力 主轴到位并在此过程中构建有组织的组织。总的来说，我们的工作目标是 了解细胞如何处理信息以特定目标极性和纺锤体方向 在正确的时间将复合物转移到细胞的适当区域，激活这些复合物一次 它们是局部的，以及这些复合物的活性如何转化为复杂的细胞 功能。 我们未来五年的目标是确定特定的分子相互作用 不对称分裂神经干细胞中 Par 复合物的极化并激活 复合物中包含的酶活性。在之前的工作中，我们确定了 Par 如何 复杂的极化其基板，我们正在尝试用它来“逆向工程” 鉴定新的极化蛋白质。该项目的前提是新知识 极化因子将帮助我们理解 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。 我们还对一种重要的极性输出特别感兴趣：有丝分裂纺锤体方向。 该项目的前提是动物细胞经常将其有丝分裂纺锤体与有丝分裂纺锤体的轴对齐。 分裂时的极性。这样做的原因之一是它控制结果的位置 子细胞，这一特征对于复杂细胞的构建和维护非常重要 组织。我们的重点是预防癌症样过度增殖所需的蛋白质。