Presence of a Putative Vesicular Inositol 1,4,5-Trisphosphate-Sensitive Nucleoplasmic Ca²⁺ Store

Abstract

The inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are widely localized in both the heterochromatin and euchromatin regions. We found recently the presence of nucleoplasmic complexes that are composed of phospholipids, IP(3)R/Ca(2+) channels, and Ca(2+) storage protein chromogranin B (CGB). Close examination and 3D image reconstruction of these complexes revealed numerous vesicular structures with an average diameter of approximately 50 nm that are primarily interspersed between the heterochromatins. IP(3) rapidly released Ca(2+) from these structures, but other inositol phosphates, inositol 1,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate, failed to release Ca(2+). Addition of heparin or IP(3)R antibody blocked the IP(3)-induced Ca(2+) releases, indicating the release of Ca(2+) through the IP(3)R/Ca(2+) channels. Given the presence of the IP(3)R/Ca(2+) channels and Ca(2+) storage protein CGB in these vesicular structures, we postulate that these vesicles are the IP(3)-sensitive nucleoplasmic Ca(2+) stores. Abundance of the vesicular Ca(2+) stores between the heterochromatins appeared to imply critical roles these vesicular Ca(2+) stores play in controlling the Ca(2+) concentrations of the chromosomes.

Role of the nuclear envelope in calcium signalling

“…Functional experiments suggest that IP 3 can induce the release of Ca 2+ directly through the INM (see below), but to our knowledge there is no immunohistochemical evidence at the EM level for the localisation of IP 3 R on the INM. It should be noted that some studies describe the presence of IP 3 R on small vesicles inside the nucleus that could be responsible for nuclear Ca 2+ transients (Huh, et al, 2006, Yoo, et al, 2005. Whether these vesicles are different from invaginations of the NE is not clear.…”

Intracellular organelles in the saga of Ca2+ homeostasis: different molecules for different purposes?

“…Some reports have even hypothesized the existence in the nucleoplasm of a pool of small vesicles containing chromogranin B and IP 3 Rs capable of accumulating and releasing Ca 2? upon stimulation [241,242].…”

Localization and projected role of phosphatidylinositol 4-kinases IIα and IIβ in inositol 1,4,5-trisphosphate-sensitive nucleoplasmic Ca2+store vesicles

“…We have demonstrated previously the existence of numerous small Ins(1,4,5) P 3 -sensitive nucleoplasmic Ca 2+ store vesicles that contain the Ins(1,4,5) P 3 Rs and PtdIns(4,5) P 2 in the nucleus 24 , 25 . The small Ins(1,4,5) P 3 -sensitive nucleoplasmic Ca 2+ store vesicles have an average diameter of ~50 nm and rapidly release Ca 2+ in response to Ins(1,4,5) P 3 25 .…”

“…The small Ins(1,4,5) P 3 -sensitive nucleoplasmic Ca 2+ store vesicles have an average diameter of ~50 nm and rapidly release Ca 2+ in response to Ins(1,4,5) P 3 25 . No other inositol phosphates including inositol 1,4-bisphosphate (IP 2 ), inositol 1,3,4-trisphoshate, and inositol 1,3,4,5-tetrakisphosphate (IP 4 ) can release Ca 2+ from these vesicles, whereby demonstrating the inositol 1,4,5-trisphosphate (Ins(1,4,5) P 3 )-specific nature of the Ca 2+ stores.…”