Presence of a nucleoplasmic complex composed of the inositol 1,4,5-trisphosphate receptor/Ca2+ channel, chromogranin B, and phospholipids.
Although the inositol 1,4,5-trisphosphate (IP(3)) induced nuclear Ca(2+) releases have been shown to play key roles in nuclear functions, the presence and operation of the IP(3)-dependent Ca(2+) control mechanism in the nucleoplasm have not been shown. Recently, we found the presence of a high-capacity, low-affinity Ca(2+)-storage protein chromogranin B (CGB) and all three IP(3) receptor (IP(3)R) isoforms in the nucleoplasm, localizing widely in both the heterochromatin and euchromatin regions. In view of the essential role of CGB-IP(3)R coupling in IP(3)-dependent Ca(2+) 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 IP(3)R, CGB, and phospholipids, with an estimated molecular mass of approximately 2-3 x 10(7) Da, suggesting the possibility of the presence of an IP(3)-sensitive Ca(2+) store in the nucleoplasm. Moreover, double-labeling immunogold electron microscope studies showed the colocalization of all three IP(3)R isoforms with CGB to the extent that the majority of each IP(3)R 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 IP(3)-dependent vesicular nucleoplasmic Ca(2+) store, our preliminary results indeed showed a sudden release of Ca(2+) from a putative nucleoplasmic Ca(2+) store in response specifically to IP(3) but not to inositol 1,4-bisphosphate or inositol 1,3,4,5-tetrakisphosphate.
Yoo
Seung Hyun
SH
National Creative Research Initiative Center for Secretory Granule Research and Department of Biochemistry, Inha University College of Medicine, Jung Gu, Incheon 400-712, Korea. shyoo@inha.ac.kr
Nam
Seong Won
SW
Huh
Seong Kwon
SK
Park
Seon Young
SY
Huh
Yang Hoon
YH
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism*; D002850:Chromatography, Gel; D002864:Chromogranins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006046:Gold / Q000737:chemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors; D046529:Microscopy, Electron, Transmission; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D015220:Calcium Channels; D002864:Chromogranins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D046912:Multiprotein Complexes; D010743:Phospholipids; D018160:Receptors, Cytoplasmic and Nuclear; D006046:Gold