Role of Nuclear Chromogranin B in Inositol 1,4,5-Trisphosphate-Mediated Nuclear Ca2+ Mobilization

• Published in: Biochemistry (Easton) Vol. 45; no. 4; pp. 1212 - 1226
• Main Authors: Huh, Yang Hoon, Chu, Sei Yoon, Park, Seon Young, Huh, Seong Kwon, Yoo, Seung Hyun
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 31.01.2006
• Subjects: Adenosine Triphosphate - agonists; Adenosine Triphosphate - metabolism; Animals; Calcium Signaling - drug effects; Calcium Signaling - physiology; Cell Nucleus - metabolism; Chromogranin A; Chromogranin B; Chromogranins - metabolism; Chromogranins - physiology; Cytoplasm - metabolism; Inositol 1,4,5-Trisphosphate - metabolism; Inositol 1,4,5-Trisphosphate - pharmacology; Mice; Microinjections; Microscopy, Confocal; Microscopy, Immunoelectron; NIH 3T3 Cells; PC12 Cells; Rats; Recombinant Proteins - metabolism; Time Factors; Transfection
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi051594r

Recently, secretory granule Ca2+ storage protein chromogranin B (CGB) was shown to be present in the nucleoplasm proper in a complex structure that consists of the inositol 1,4,5-trisphosphate receptor (IP3R)/Ca2+ channels and the phospholipids. Further, the amounts of IP3Rs present in the nucleus of bovine chromaffin cells were shown to be comparable to that of the endoplasmic reticulum. Therefore, we investigated here the potential contribution of nuclear CGB on the IP3-dependent Ca2+ mobilization in the nucleus, using both neuroendocrine PC12 and nonneuroendocrine NIH3T3 cells. Chromogranin A (CGA) expression in the NIH3T3 cells, which do not contain intrinsic chromogranins, increased the IP3-induced Ca2+ releases in the nucleus by 45%, while CGB expression in the same cells increased the IP3-induced Ca2+ releases in the nucleus by 80%. Microinjection of IP3 into the nucleus of CGB-expressing NIH3T3 cells increased the IP3-dependent nuclear Ca2+ mobilization ∼3-fold, whereas in CGA-expressing cells it remained the same as that of control cells. In contrast, inhibition of CGA expression in PC12 cells by siRNA treatment decreased the IP3-induced Ca2+ releases in the nucleus by 17%, while inhibition of CGB expression decreased the IP3-induced Ca2+ releases in the nucleus by 55%. Microinjection of IP3 into the nucleus of siCGB-treated PC12 cells decreased the IP3-dependent nuclear Ca2+ mobilization by ∼75%, whereas in siCGA-treated cells it remained the same as that of control cells. Given the presence of CGB in the nucleus, these results further highlight the critical contribution of nuclear CGB in the IP3-induced Ca2+ release in the nucleus.