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首页> 外文期刊>Biochemistry >Presence of a nucleoplasmic complex composed of the inositol 1,4,5-trisphosphate receptor/Ca2+ channel, chromogranin B, and phospholipids
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Presence of a nucleoplasmic complex composed of the inositol 1,4,5-trisphosphate receptor/Ca2+ channel, chromogranin B, and phospholipids

机译:由肌醇1,4,5-三磷酸受体/ Ca2 +通道,嗜铬粒蛋白B和磷脂组成的核质复合物的存在

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Although the inositol 1,4,5-trisphosphate (IP3) induced nuclear Ca2+ releases have been shown to play key roles in nuclear functions, the presence and operation of the IP3-dependent Ca2+ control mechanism in the nucleoplasm have not been shown. Recently, we found the presence of a high-capacity, low-affinity Ca2+-storage protein chromogranin B (CGB) and all three IP3 receptor (IP3R) isoforms in the nucleoplasm, localizing widely in both the heterochromatin and euchromatin regions. In view of the essential role of CGB-IP3R coupling in IP3-dependent Ca2+ release in the endoplasmic reticulum, the potential coupling between CGB and the IP(3)Rs in the nucleoplasm was investigated. Hence, we found in the present study the presence of a nucleoplasmic complex, which is composed of the IP3R, CGB, and phospholipids, with an estimated molecular mass of similar to 2-3 x 10(7) Da, suggesting the possibility of the presence of an IP3-sensitive Ca2+ store in the nucleoplasm. Moreover, double-labeling immunogold electron microscope studies showed the colocalization of all three IP3R isoforms with CGB to the extent that the majority of each IP3R isoform-labeling gold particles found in the nucleoplasm was literally next to the CGB-labeling gold particles. In line with the potential existence of an IP3-dependent vesicular nucleoplasmic Ca2+ store, our preliminary results indeed showed a sudden release of Ca2+ from a putative nucleoplasmic Ca2+ store in response specifically to IP3 but not to inositol 1,4-bisphosphate or inositol 1,3,4,5-tetrakisphosphate.
机译:尽管已显示肌醇1,4,5-三磷酸(IP3)诱导的核Ca2 +释放在核功能中起关键作用,但尚未显示出IP3依赖性Ca2 +控制机制在核质中的存在和运行。最近,我们发现在核质中存在高容量,低亲和力的Ca2 +存储蛋白嗜铬粒蛋白B(CGB)和所有三个IP3受体(IP3R)同工型,广泛分布于异染色质和常染色质区域。鉴于CGB-IP3R偶联在内质网中IP3依赖性Ca2 +释放中的重要作用,研究了CGB与核质中IP(3)Rs之间的潜在偶联。因此,我们在本研究中发现存在由IP3R,CGB和磷脂组成的核仁复合物,其估计分子量约为2-3 x 10(7)Da,这表明存在这种可能性。 IP3敏感的Ca2 +存储在核质中的存在。此外,双标记免疫金电子显微镜研究显示,所有三种IP3R同工型与CGB的共定位程度,使得在核质中发现的每个IP3R同工型标记的金颗粒中的大部分实际上都紧邻CGB标记金颗粒。与IP3依赖的囊泡核质Ca2 +存储库的潜在存在相符,我们的初步结果确实显示,Ca2 +从推定的核质Ca2 +存储库中突然释放,是对IP3的特异性反应,而不是对肌醇1,4-双磷酸或肌醇1的响应。 3,4,5-四磷酸。

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