INOSITOL 1,4,5 TRIPHOSPHATE RECEPTOR (IP3R)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肌醇1，4，5-三磷酸受体(IP3Rs)是由1，4，5-三磷酸(IP3)调控的细胞内钙释放通道。这些通道允许内质网中的钙离子快速流动，从而在神经递质释放、受精、激素分泌、基因转录、代谢调节和细胞凋亡中发挥关键作用。 在哺乳动物中，表达了3个不同的IP3R基因，其同源性约为70%。单个细胞类型可以表达多种异构体，它们可以形成同源或异源四聚体群体。I型IP3R(IP3R1)是小脑内质网(ER)中的主要类型，形成同源四聚体，MR大于1.2mda。小脑通常被用作纯化IP3R1的主要来源，用于结构和功能的表征。该项目的长期目标是通过对IP3R通道复合体的结构和功能的分析，确定IP3诱导的钙门控的分子机制，并确定该通道蛋白的缺陷如何导致与人类疾病相关的细胞钙水平的异常调节，这些疾病包括心肌肥厚、心力衰竭、遗传性共济失调、骨质疏松症、动脉粥样硬化和一些偏头痛。

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. Inositol 1,4,5-trisphosphate receptors (IP3Rs) are the intracellular Ca2+ release channels gated by inositol 1,4,5-trisphosphate (IP3). These channels allow rapid fluxes of Ca2+ ions from the endoplasmic reticulum, thereby playing a key role in neurotransmitter release, fertilization, hormone secretion, gene transcription, metabolic regulation and apoptosis. In mammals, 3 different IP3R genes, sharing ~70% homology, are expressed. Individual cell types can express more than one isoform, and they may form homo- or hetero-tetrameric populations. The type 1 IP3R (IP3R1) is the predominant type in the cerebellar endoplasmic reticulum (ER), forming homo-tetramers with a Mr over 1.2 MDa. The cerebellum is generally used as a primary source for purification of the IP3R1 for structure-function characterization. The long-term objectives of this project are to determine the molecular mechanisms of the IP3-induced Ca2+-gating through structure-function analysis of the IP3R channel complex and to define how defects in this channel protein can cause abnormal regulation of cell Ca2+ level underlying human diseases such as cardiac hypertrophy, heart failure, hereditary ataxias, osteoporosis, atherosclerosis and some migraines.