STRUCTURAL AND FUNCTIONAL STUDIES OF INOSITOL PHOSPHATASES

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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.