Molecular mechanisms underlying the generation of spatiotemporal patterns of cytoplasmic calcium

1，4，5-三磷酸肌醇(IP_3)是磷脂酰肌醇信号转导系统对激素、神经递质和生长因子级联反应产生的第二信使，通过与IP_3受体(IP_3R)结合，引起细胞内钙离子释放。IP_3受体是IP_3门控的细胞内钙释放通道。胞浆内钙离子的释放存在复杂的时空模式，如钙波动和钙振荡，并调节许多细胞反应，包括受精、肌肉收缩、分泌、细胞生长、分化、细胞凋亡和突触可塑性。在本研究中，我们从小鼠肺中分离了编码2型和3型IP_3R的cDNA，发现每种类型的受体都以不同的亲和力和协同性与IP_3结合。我们还发现，用ATP刺激钙离子载体可以诱导COS-7细胞中表达的三种类型的小鼠IP_3R形成簇，并且刺激诱导的簇的大小和形状在三种类型的IP_3R中不同。三种IP_3R类型对IP_3反应的差异性和细胞内分布的差异可能有助于细胞质Ca~(2+)和Gt~(2+)的复杂时空模式的产生。

Inositol 1,4,5-trisphosphate (IP_3) is a second messenger generated by the phosphatidylinositol signaling cascade response to hormones, neurotransmitters, and growth factors and causes Ca^<2+> release from intracellular stores by binding to the IP_3 receptor (IP_3R), which is an IP_3-gated intracellular Ca^<2+> release channel. Ca^<2+> release in the cytoplasm occurs in complex spatial and temporal patterns, such as Ca^<2+> waves and Ca^<2+> oscillations, and regulates many cellular responses, including fertilization, muscle contraction, secretion, cell growth, differentiation, apoptosis, and synaptic plasticity. In this research, we isolated cDNAs encoding type 2 and type 3 IP_3R from mouse lung and found that each type of receptor binds IP_3 with different affinity and cooperativity. We also found that stimulation with ATP of Ca^<2+> ionophore induced cluster formation of all three types of mouse IP_3R expressed in COS-7 cells and that the size and shape of stimulus-induced clusters differ among the three types of IP_3R. The diversity of responsiveness to IP_3 and the intracellular distribution observed among the three IP_3R types may contribute to the generation of the complex spatiotemporal patterns of cytoplasmic Ca^<2+>.