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Inositol 1,4,5-Trisphosphate Receptor in Chromaffin Secretory Granules and Its Relation to Chromogranins

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A Commentary to this article was published on 19 November 2010

Abstract

The inositol 1,4,5-trisphosphate (IP3)-mediated intracellular Ca2+ releases in secretory cells play vital roles in controlling not only the intracellular Ca2+ concentrations but also the Ca2+-dependent exocytotic processes. Of intracellular organelles that release Ca2+ in response to IP3, secretory granules stand out as the most prominent organelle and are responsible for the majority of IP3-dependent Ca2+ releases in the cytoplasm of chromaffin cells. Bovine chromaffin granules were the first granules that demonstrated the IP3-mediated Ca2+ release as well as the presence of the IP3 receptor (IP3R) in granule membranes. Secretory granules contain all three (type 1, 2, and 3) IP3R isoforms, and 58–69% of total cellular IP3R isoforms are expressed in bovine chromaffin granules. Moreover, secretory granules contain large amounts (2–4 mM) of chromogranins and secretogranins; chromogranins A and B, and secretogranin II being the major species. Chromogranins A and B, and secretogranin II are high-capacity, low-affinity Ca2+ binding proteins, binding 30–93 mol of Ca2+/mol of protein with dissociation constants of 1.5–4.0 mM. Due to this high Ca2+ storage properties of chromogranins secretory granules contain ~40 mM Ca2+. Furthermore, chromogranins A and B directly interact with the IP3Rs and modulate the IP3R/Ca2+ channels, i.e., increasing the open probability and the mean open time of the channels 8- to 16-fold and 9- to 42-fold, respectively. Coupled chromogranins change the IP3R/Ca2+ channels to a more ordered, release-ready state, whereby making the IP3R/Ca2+ channels significantly more sensitive to IP3.

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Acknowledgment

The present work was supported in part by the CRI Program and BK21 Program (YSH) of the Republic of Korea.

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  1. Department of Biochemistry, Inha University School of Medicine, Jung Gu, Incheon, 400-712, Korea

    Seung Hyun Yoo, Yang Hoon Huh & Yong Suk Hur

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  1. Seung Hyun Yoo
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  2. Yang Hoon Huh
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Correspondence to Seung Hyun Yoo.

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A commentry to this article can be found at doi:10.1007/s10571-010-9552-6.

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Yoo, S.H., Huh, Y.H. & Hur, Y.S. Inositol 1,4,5-Trisphosphate Receptor in Chromaffin Secretory Granules and Its Relation to Chromogranins. Cell Mol Neurobiol 30, 1155–1161 (2010). https://doi.org/10.1007/s10571-010-9564-2

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