Study of IP_3 receptor/Ca^<2+> signaling in neural plasticity and brain development and differentiation

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IP_3 is important in cell signaling but requires the IP_3 receptor (IP_3R) to mediate all of its effects. Structural and biochemical studies indicate that the IP_3R provides a platform for molecules to interact, and combinations of associated molecules results which we discovered such as ERp44, GRP78, 80K-H et al, in functional diversity of cell signaling. IP_3Rs determine the trajectory of cell signaling by working as a signaling hub for interaction with differential molecular complexes which we discovered for various cell functions. The IP_3R signaling trajectory, in turn, plays a crucial role in cellular functions, in addition, IRBIT which is released from IP_3R as 3^<rd> messenger, also plays a variety of role. The abnormality of IP_3R signaling results in diseases such as neuronal degeneration, learning deficient, cardiogenesis abnormality, osteoporosis, auto-immune-disease, acute pancreatitis. We have developed ultra-sensitive genetically encoded Ca^<2+> indicator, Ca^<2+> pump indicator and established in vivo imaging of the cerebellum and cerebral cortex by two photon microscopy to study more in detail.