Receptor Phosphatases and Process Outgrowth

描述（由申请人提供）：许多发展的一个关键方面 细胞类型，特别是神经元，它们必须将投射延伸到 长距离和不同的地形，以便与适当的 目标的为了实现这一目标，投影在其表面上进行 这些分子使它们能够检测到外部信号并做出适当的反应。 这里提出的工作旨在了解一种特殊的分子， 我们已经鉴定并命名为HmLAR2的受体磷酸酶， 功能受体磷酸酶在从果蝇到 大鼠，作为信号通路的关键组成部分， 在特定的方式对环境因素，既可溶性和结合到其他 细胞或细胞外基质。我们计划研究细胞的动力学 当HmLAR2被实验干扰或删除时，生长受到影响，或 在正常情况下不表达相应的 基因已经识别出相关的外部信号以及 可能介导该分子如何影响细胞的推定内部底物 增长，我们现在寻求进一步了解其作用机制，使用 准备，药用水蛭，允许非常精细的实时成像， 完整的活胚胎中的单个细胞。在 到目前为止，我们已经了解到这种分子对于 在一种特殊的 我们还试图建立这种普遍性， 通过研究，在同一系统中，其他细胞也表达这种 分子。我们的长期目标是详细了解 HmLAR2是其中一员的分子途径，以了解这种分子如何 是由细胞调节的，为了解释它是如何在分子水平上 其功能是将外部信号转换为内部响应。这 详细的知识水平将使我们了解如何病理 影响这类重要表面受体功能的状态可 导致包括神经在内的组织和器官的发育中断 和肌肉组织，这是代表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.