Nuclear inositol 1,4,5-trisphosphate receptors regulate local Ca2+ transients and modulate cAMP response element binding protein phosphorylation
Nuclear inositol 1,4,5-trisphosphate receptors regulate local Ca2+ transients and modulate cAMP response element binding protein phosphorylation
复制标题
DOI：
10.1242/jcs.02446
复制
发表时间：
2005-07-15
影响因子：
4
通讯作者：
Jaimovich, E
中科院分区：
文献类型：
--
作者：
Cárdenas, C;Liberona, JL;Jaimovich, E
一些证据表明，核Ca2+的增加具有不同于胞质Ca2+的特定生物学效应，表明它们是独立发生的。参与控制核Ca2+信号的机制既有争议，也仍然知之甚少。利用低渗休克联合机械破坏，我们从培养的大鼠骨骼肌管中获得了纯化核的一部分并对其进行了表征。免疫印迹研究和放射性标记肌醇1,4,5-三磷酸[IP3]结合均显示核部分中IP3受体的重要浓度。免疫荧光和免疫电镜研究了核内定位的1型和3型IP3受体，其中1型受体优先定位于核膜内。2型IP3受体局限于肌浆网。离体细胞核对IP3的反应是快速和短暂的Ca2+浓度升高，这被已知的IP3信号阻滞剂抑制。从1B5细胞系分离的细胞核中获得了类似的结果，该细胞系不表达ryanodine受体，但以ip3依赖的方式释放核Ca2+。IP3触发的核Ca2+增加诱发cAMP反应元件结合蛋白磷酸化，其动力学与顺序激活相一致。这些结果支持Ca2+信号，由肌细胞的核IP3受体介导，是一个独特的Ca2+释放成分的一部分，起源于细胞核，可能参与cAMP反应元件结合蛋白介导的基因调控。
Several lines of evidence indicate that increases in nuclear Ca2+ have specific biological effects that differ from those of cytosolic Ca2+, suggesting that they occur independently. The mechanisms involved in controlling nuclear Ca2+ signaling are both controversial and still poorly understood. Using hypotonic shock combined with mechanical disruption, we obtained and characterized a fraction of purified nuclei from cultured rat skeletal myotubes. Both immunoblot studies and radiolabeled inositol 1,4,5-trisphosphate [IP3] binding revealed an important concentration Of IP3 receptors in the nuclear fraction. Immunofluorescence and immunoelectron microscopy studies localized type-1 and type-3 IP3 receptors in the nucleus with type-1 receptors preferentially localized in the inner nuclear membrane. Type-2 IP3 receptor was confined to the sareoplasmic reticulum. Isolated nuclei responded to IP3 with rapid and transient Ca2+ concentration elevations, which were inhibited by known blockers Of IP3 signals. Similar results were obtained with isolated nuclei from the 1B5 cell line, which does not express ryanodine receptors but releases nuclear Ca2+ in an IP3-dependent manner. Nuclear Ca2+ increases triggered by IP3 evoked phosphorylation of cAMP response element binding protein with kinetics compatible with sequential activation. These results support the idea that Ca2+ signals, mediated by nuclear IP3 receptors in muscle cells, are part of a distinct Ca2+ release component that originates in the nucleus and probably participates in gene regulation mediated by cAMP response element binding protein.