Inositol 1,4,5-Trisphosphate Receptor/Ca2+Channel Modulatory Role of Chromogranin A, a Ca2+Storage Protein of Secretory Granules*

Inositol 1,4,5-Trisphosphate Receptor/Ca2+Channel Modulatory Role of Chromogranin A, a Ca2+Storage Protein of Secretory Granules*
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肌醇 1,4,5-三磷酸受体/Ca2 通道嗜铬素 A 的调节作用,一种分泌颗粒的 Ca2 储存蛋白*

DOI:
10.1074/jbc.m909391199
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发表时间:
2000
期刊:
The Journal of Biological Chemistry
影响因子:
--
通讯作者:
C. J. Jeon
C. J. Jeon
中科院分区:
--
文献类型:
--
作者:
S. Yoo;C. J. Jeon

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神经内分泌细胞的分泌颗粒含有大量的Ca ~(2+)和嗜铬粒蛋白,它们对1,4,5-三磷酸肌醇(IP_3)的反应是释放Ca ~(2+),表明分泌颗粒具有IP_3敏感的胞内Ca ~(2+)储存功能。在我们以前的研究中,嗜铬粒蛋白A(CGA)显示在囊泡内pH 5.5时与几种分泌颗粒膜蛋白,包括IP 3受体(IP 3R)相互作用(Yoo,S. H.(1994)J.Biol.Chem.269,12001-12006)。为了检查这种偶联的功能方面,我们测量了在存在和不存在CGA的情况下重构到脂质体中的IP 3R的IP 3介导的Ca 2+释放性质。CGA在IP 3R重构脂质体中的存在显著增强了IP 3介导的Ca 2+从脂质体的释放。此外,与重组的IP 3R结合的IP 3的数量增加。荧光能量转移和IP 3R Trp荧光猝灭研究表明,重构的IP 3R的结构变得更加有序,并暴露在CGA的存在下,这表明脂质体中的偶联CGA引起IP 3R的结构变化,将其改变为更适合IP 3结合和随后的Ca 2+释放的结构。这些结果似乎强调了分泌颗粒中IP 3R-CGA偶联的生理意义。
The secretory granules of neuroendocrine cells, which contain large amounts of Ca2+ and chromogranins, have been demonstrated to release Ca2+ in response to inositol 1,4,5-trisphosphate (IP3), indicating the IP3-sensitive intracellular Ca2+ store role of secretory granules. In our previous study, chromogranin A (CGA) was shown to interact with several secretory granule membrane proteins, including the IP3 receptor (IP3R), at the intravesicular pH 5.5 (Yoo, S. H. (1994) J. Biol. Chem. 269, 12001–12006). To examine the functional aspect of this coupling, we measured the IP3-mediated Ca2+ release property of the IP3R reconstituted into liposomes in the presence and absence of CGA. Presence of CGA in the IP3R-reconstituted liposome significantly enhanced the IP3-mediated Ca2+ release from the liposomes. Moreover, the number of IP3 bound to the reconstituted IP3R increased. The fluorescence energy transfer and IP3R Trp fluorescence quenching studies indicated that the structure of reconstituted IP3R becomes more ordered and exposed in the presence of CGA, suggesting that the coupled CGA in the liposome caused structural changes of the IP3R, changing it to a structure that is better suited to IP3 binding and subsequent Ca2+ release. These results appear to underscore the physiological significance of IP3R-CGA coupling in the secretory granules.
DOI: 10.1016/s0021-9258(18)77318-3
发表时间: 1990-08
期刊: The Journal of biological chemistry
影响因子: --
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DOI: --
发表时间: 1991
期刊: The Journal of biological chemistry
影响因子: --
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