STRUCTURAL AND FUNCTIONAL STUDIES OF INOSITOL PHOSPHATASES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这个建议的具体目标是研究肌醇磷酸酶的结构和功能，去磷酸化磷酸肌醇。 这些是含有多结构域的蛋白质，具有位于催化结构域侧翼的几个辅助结构域。 辅助结构域负责这些酶在细胞内的空间和时间调节。 我们的实验室感兴趣的是识别这些结构域的结合伙伴，并在这些相互作用的结构基础的表征。鉴于磷酸肌醇在细胞信号传导和膜动力学中的重要作用，这些研究具有广泛的细胞生物学意义，并且与我们实验室的主要关注点膜交通领域高度相关。 此外，磷脂酰肌醇代谢异常还与病原体侵袭、癌症、糖尿病和多种遗传性疾病如Lowe综合征、肌管性肌病、Charcot-Marie Tooth病等有关。因此，我们的研究可能有助于进一步阐明这些疾病的机制，并可能指出新的治疗干预策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific objective of this proposal is to investigate the structure and function of inositol phosphatases that dephosphorylate phosphoinositides. These are multi-domain containing proteins with several accessory domains flanking the catalytic domain. The accessory domains are responsible for the spatial and temporal regulation of these enzymes within cells. Our lab is interested in the identification of binding partners for these domains and in the characterization of the structural bases of these interactions. Given the important role of phosphoinositides in cell signaling and membrane dynamics, these studies have broad cell biological interest, and are highly relevant to the field of membrane traffic, a main focus of our lab. In addition, abnormal phosphoinositide metabolism is implicated in pathogen invasion, cancer, diabetes and a variety of hereditary diseases, such as Lowe syndrome, myotubular myopathy, Charcot-Marie Tooth disease. Thus, our studies may help to further elucidate mechanisms in these diseases and may point to new strategies for therapeutic interventions.