Molecular mechanisms that regulate polarity and spindle orientation in animals

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 薄膜。例如，排列在我们消化道的细胞准备吸收营养。 从细胞的一侧将它们传递到身体另一侧的其他部位。这项建议 检查PAR复合体的活性，PAR复合体是一组负责创建和 维持动物细胞膜的不同区域。我们还在研究细胞如何 不对称性转化为在动物组织和器官中看到的复杂组织。 在组织内创建结构的一种机制是控制细胞的放置，该细胞 是一个分裂的结果。这可以通过定位有丝分裂纺锤体--该装置 在分裂过程中沿着特定的轴分离染色体。我们正在决定如何 细胞膜的某些区域招募分子马达，这些马达产生旋转 在此过程中，将纺锤固定到位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，以特定fi为目标的极性和纺锤体方向 在正确的时间将这些复合体连接到细胞的适当区域，一次激活这些复合体 它们是局部化的，以及这些复合体的活性如何转化为复杂的细胞 功能。 我们在接下来的fi五年中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复合体的极化并激活 复合体中所含的酶活性。在之前的工作中，我们确定了平价如何 复杂的极化其衬底，我们正试图利用这一点“反向工程” 识别新的极化蛋白的fi阳离子。这个项目前提是对新知识的了解 极化因素将帮助我们理解PAR极性是如何转化为函数的，例如 在我们消化系统的上皮细胞中发现了极化运输。 我们还特别对一种重要的极性输出感兴趣：有丝分裂的纺锤体取向。 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 分裂过程中的极性。这样做的一个原因是它控制产生的 子代细胞，这一特征对于建筑群的构建和维护非常重要 纸巾。我们的重点是一种蛋白质，这种蛋白质是防止类似癌症的过度增殖所必需的。

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.