The role of Ca2+ signaling in cell function with special reference to exocrine secretion
The role of Ca2+ signaling in cell function with special reference to exocrine secretion
复制标题
DOI：
10.1097/ico.0b013e31817f246e
复制
发表时间：
2008-09-01
期刊：
影响因子：
2.8
通讯作者：
Miyachi, Kiyomitsu
中科院分区：
文献类型：
--
作者：
Mikoshiba, Katsuhiko;Hisatsune, Chihiro;Miyachi, Kiyomitsu
肌醇1，4，5-三磷酸（IP 3）是诱导钙从内质网（ER）释放的第二信使。IP 3受体被发现是一种发育调节的糖磷蛋白，P400，在突变小鼠品系中不存在。IP 3受体的IP 3结合核心和N-末端抑制序列的晶体结构已被确定。IP 3结合核心对IP 3的亲和力在IP 3受体的三种亚型之间是相似的;然而，N-末端IP 3结合抑制区负责亚型特异性IP 3结合亲和力的调节。已经鉴定了IP 3受体运输的各种途径;例如，ER形成网状结构，IP 3受体通过侧向扩散在该网状结构上移动，并且含有IP 3受体的囊泡ER亚室使用驱动蛋白马达沿着微管快速移动。此外，信使RNA颗粒内的IP 3受体信使RNA也沿沿着微管移动。最近，我们发现IP 3受体在外分泌中起着至关重要的作用。ERp 44作为ER中的氧化还原传感器起作用，并调节IP 3 1型受体活性。IP 3受体还释放与IP 3一起释放的IP 3受体结合蛋白（伊尔比特）。伊尔比特是IP 3的假配体，通过IP 3受体调节钙振荡的频率和振幅。伊尔比特与胰腺型碳酸氢钠协同转运蛋白1结合，后者对酸碱平衡很重要。2型和3型双缺陷小鼠表现出唾液、泪液和胰液分泌的缺陷。1型IP 3受体影响脑源性神经营养因子的产生
Inositol 1,4,5-trisphosphate (IP3) is a second messenger that induces the release of calcium from the endoplasmic reticulum (ER). The IP3 receptor was discovered as a developmentally regulated glycophosphoprotein, P400, that is absent in strains of mutant mice. The crystal structures of the IP3-binding core and N-terminal suppressor sequence of the IP3 receptor have been identified. The IP3-binding core's affinity to IP3 is similar among the three isoforms of IP3 receptors; however, the N-terminal IP3-binding suppressor region is responsible for isoform-specific IP3-binding affinity tuning. Various pathways for the trafficking of IP3 receptors have been identified; for example, the ER forms a meshwork on which IP3 receptors move by lateral diffusion, and vesicular ER subcompartments containing IP3 receptors move rapidly along microtubules using a kinesin motor. Furthermore, IP3 receptor messenger RNA within messenger RNA granules also moves along microtubules. Recently, we discovered that IP3 receptors play a crucial role in exocrine secretion. ERp44 works as a redox sensor in the ER and regulates IP3 type 1 receptor activity. IP3 receptor also releases IP3 receptor-binding protein released with IP3 (IRBIT). IRBIT is a pseudoligand for IP3 that regulates the frequency and amplitude of calcium oscillations through the IP3 receptor. IRBIT binds to pancreas-type sodium bicarbonate cotransporter 1, which is important for acid-base balance. Type 2 and 3 double-deficient mice show a deficit in saliva and lacrimal and pancreatic juice secretion. Type 1 IP3 receptor influences brain-derived neurotrophic factor production.