Receptor Phosphatases and Process Outgrowth

描述(由申请人提供)：多项发展的关键方面 细胞的类型，特别是神经元，它们必须将投射延伸到 远距离和不同的地形，以便与适当的 目标。为了实现这一目标，投影在它们的表面上进行 使它们能够检测并对外部提示做出适当反应的分子。 这里提出的工作试图理解一种特定的分子是如何， 我们已经鉴定并命名为HmLAR2的一种受体磷酸酶执行这一任务 功能。受体磷酸酶已被牵连，在从苍蝇到 老鼠，作为允许细胞做出反应的信号通路的关键组件 在特定的环境因素中，既能溶解又能结合其他 细胞或细胞外基质。我们计划研究细胞动力学是如何 当HmLAR2被实验性干扰或删除时，生长会受到影响，或者 在通常不表达相应基因的细胞中异位表达 吉恩。在已经识别出相关的外部信号以及 推测的内部底物，可能介导该分子如何影响细胞 增长，我们现在试图通过使用一个 制剂，药用水蛭，允许非常精细的实时成像 在复杂的显微镜下，完整的活胚胎中的单个细胞。在……里面 到目前为止的实验我们已经了解到，这种分子对 一种特殊类型的迁移结构的生长和维护 表达它的细胞。我们还试图确立这一点的普遍性。 通过研究同一系统中也表达这一点的其他细胞进行观察 分子。我们的长远目标是详细了解 HmLAR2是其成员的分子途径，以了解该分子是如何 是由细胞调节的，并从分子的角度解释它是如何实现 它的功能是将外部信号转换为内部反应。这 详细的知识水平将使我们能够理解病理性 影响这类重要表面受体功能的状态可能 导致组织和器官发育的崩溃，包括神经 和肌肉组织，这代表了某些类型的人类疾病 条件。

DESCRIPTION (provided by applicant): A key aspect of the development of many types of cells, particularly neurons, is that they must extend projections over long distances and varied terrains in order to interact with appropriate targets. In order to achieve this goal, projections carry on their surfaces molecules that allow them to detect and respond appropriately to external cues. The work proposed here seeks to understand how one particular kind of molecule, a receptor phosphatase we have identified and named HmLAR2, performs this function. Receptor phosphatases have been implicated, in systems from flies to rats, as key components of the signaling pathways that allow cells to respond in specific ways to environmental factors, both soluble and bound to other cells or extracellular matrices. We plan to examine how the dynamics of cell growth are affected when HmLAR2 is experimentally perturbed or deleted, or expressed ectopically in cells that normally do not express the corresponding gene. Having already identified a relevant external signal as well as a putative internal substrate that could mediate how this molecule affects cell growth, we now seek to understand further its mechanisms of action by using a preparation, the medicinal leech, that allows very refined live imaging of individual cells in the intact living embryo with sophisticated microscopes. In experiments up to this point we have learned that this molecule is critical for growth and the maintenance of migrating structures in one particular kind of cell that expresses it. We also seek to establish the generality of this observation by studying, in the same system, other cells that also express this molecule. Our long-term objective is to obtained detailed knowledge of the molecular pathways of which HmLAR2 is a member, to understand how this molecule is regulated by the cell, and to explain how, in molecular terms, it achieves its function as a transducer of external signals into internal responses. This detailed level of knowledge will then allow us to understand how pathological states that affect the function of this important class of surface receptor may lead to a breakdown in the development of tissues and organs, including nerve and muscle tissues, that is representative of some types human disease conditions.