Calcium entry into the inositol 1,4,5-trisphosphate-releasable calcium pool is mediated by a GTP-regulatory mechanism.
Calcium entry into the inositol 1,4,5-trisphosphate-releasable calcium pool is mediated by a GTP-regulatory mechanism.
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钙进入肌醇 1,4,5-三磷酸盐可释放钙库是由 GTP 调节机制介导的。
DOI：
10.1073/pnas.85.8.2499
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发表时间：
1988
影响因子：
11.1
通讯作者：
Gill,DL
中科院分区：
文献类型：
--
作者：
Mullaney,JM;Yu,M;Ghosh,TK;Gill,DL
由肌醇1,4,5-三磷酸（InsP3）激活的细胞内Ca2+释放在细胞内Ca2+信号传导中起关键作用。结果表明，可释放的insp3 Ca2+池直接受到gtp调控的特异性和敏感的Ca2+转运过程的修饰，从而提出了一种控制insp3诱导Ca2+运动的机制。通过皂苷渗透的N1E-115神经母细胞瘤细胞或ddt1nf -2平滑肌源性细胞，InsP3释放30-50%的Ca2+，这些Ca2+是通过细胞内高亲和力atp依赖性Ca2+泵送活性积累的。草酸促进的Ca2+摄取被InsP3逆转，表明草酸对InsP3释放池的渗透性，这与内质网是一致的。GTP（10微米）可以激活细胞中积累的50-70%的Ca2+的释放。在5-10 mM草酸盐存在下，GTP诱导双相Ca2+通量响应；最初（1-2分钟），GTP诱导Ca2+快速释放，随后Ca2+摄取显著增加。因此，gtp激活的Ca2+内流和外排争夺Ca2+进入草酸渗透Ca2+池。InsP3和GTP的非加性作用表明，InsP3从GTP释放池的一个亚室释放Ca2+。最重要的是，在草酸存在的情况下，观察到InsP3阻断了GTP激活的摄取阶段，这表明GTP诱导Ca2+进入池，从而激活了InsP3的释放。因此，结果提供了直接的证据，证明Ca2+加载到insp3敏感的Ca2+池是由gtp调节的Ca2+转运机制控制的。这一过程可能在调节insp3诱导的Ca2+信号的程度和持续时间方面具有重要意义，而Ca2+信号是肌醇磷脂信号通路的关键步骤。
Intracellular Ca2+ release activated by inositol 1,4,5-trisphosphate (InsP3) plays a pivotal role in Ca2+ signaling in cells. A controlling mechanism for InsP3-induced Ca2+ movements is suggested by results showing that the InsP3-releasable Ca2+ pool is directly modified by a specific and sensitive GTP-regulated Ca2+-translocating process. By using saponin-permeabilized N1E-115 neuroblastoma cells or DDT1MF-2 smooth muscle-derived cells, InsP3 releases 30-50% of Ca2+ accumulated through intracellular high-affinity ATP-dependent Ca2+-pumping activity. Oxalate-promoted Ca2+ uptake is reversed by InsP3, indicating oxalate permeability of the InsP3-releasable pool, which is consistent with this compartment being the endoplasmic reticulum. GTP (10 microM) activates release of 50-70% of accumulated Ca2+ from cells. In the presence of 5-10 mM oxalate, GTP induces a biphasic Ca2+ flux response; initially (1-2 min) GTP induces rapid Ca2+ release followed thereafter by a profound increase in Ca2+ uptake. Thus, GTP-activated Ca2+ influx and efflux compete for Ca2+ access to the oxalate-permeable Ca2+ pool. The nonadditive effects of InsP3 and GTP suggest that InsP3 releases Ca2+ from a subcompartment of the GTP-releasable pool. Most significantly, InsP3 is observed to block the GTP-activated uptake phase in the presence of oxalate, indicating that GTP induces Ca2+ entry into the pool from which InsP3 activates release. Hence, the results provide direct evidence that loading of Ca2+ into the InsP3-sensitive Ca2+ pool is controlled by a GTP-regulated Ca2+-translocating mechanism. Such a process could be significant in regulating the extent and duration of the InsP3-induced Ca2+ signal, a crucial step in the inositol phospholipid signaling pathway.