INOSITOL 1,4,5 TRIPHOSPHATE RECEPTOR (IP3R)

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来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 肌醇1，4，5-三磷酸受体（Inositol 1，4，5-trisphosphate receptor，IP 3Rs）是由肌醇1，4，5-三磷酸（inositol 1，4，5-trisphosphate，IP 3）门控的细胞内钙释放通道。这些通道允许Ca 2+离子从内质网快速流出，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3种不同的IP 3R基因，具有约70%的同源性。单个细胞类型可以表达一种以上的同种型，并且它们可以形成同源或异源四聚体群体。1型IP 3R（IP 3R 1）是小脑内质网（ER）中的主要类型，形成Mr超过1.2 MDa的同源四聚体。小脑通常用作纯化IP 3 R1以进行结构-功能表征的主要来源。本项目的长期目标是通过IP 3R通道复合物的结构-功能分析确定IP 3诱导的Ca 2+门控的分子机制，并确定该通道蛋白的缺陷如何导致细胞Ca 2+水平的异常调节，这些细胞Ca 2+水平是人类疾病如心脏肥大、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的基础。

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.