Inositol 1,4,5-trisphosphate receptor is located to the inner nuclear membrane vindicating regulation of nuclear calcium signaling by inositol 1,4,5-trisphosphate - Discrete distribution of inositol phosphate receptors to inner and outer nuclear membranes
Inositol 1,4,5-trisphosphate receptor is located to the inner nuclear membrane vindicating regulation of nuclear calcium signaling by inositol 1,4,5-trisphosphate - Discrete distribution of inositol phosphate receptors to inner and outer nuclear membranes
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DOI：
10.1074/jbc.271.1.478
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发表时间：
1996-01-05
影响因子：
4.8
通讯作者：
Malviya, AN
中科院分区：
文献类型：
--
作者：
Humbert, JP;Matter, N;Malviya, AN
核内钙离子浓度的一过性升高与调控基因表达的事件有关，钙离子转运到核内的机制一直备受争议，肌醇-1，4，5-三磷酸(InSP(3))和肌醇-1，3，4，5-四磷酸肌醇(InSP(4))受体已定位于核内，它们在核内钙信号中的作用已被提出，核外膜与核内膜分离。标记酶活性、抗层粘连抗体免疫印迹、电子显微镜、Insp(4)受体和Ca~(2+)-ATPase定位于外核膜，证明两种膜制剂尽可能无交叉污染。InSP(3)受体定位于内核膜。ATP或InSP(4)诱导的胞核钙摄取，细胞外游离钙浓度，决定了ATP或InSP(4)介导的钙转运的选择。我们提出了一个核钙转运的机制模型。根据这个模型，钙可以通过ATP或InSP(4)的作用到达核膜。然而，从核膜到核质的钙释放是由Insp(3)通过激活位于核内膜的Insp(3)受体来介导的。Insp(3)在此过程中的作用是瞬时的和瞬时的，对肝素敏感。
Transient rise in nuclear calcium concentration is implicated in the regulation of events controlling gene expression, Mechanism by which calcium is transported to the nucleus is vehemently debated, Inositol 1,4,5-trisphosphate (InsP(3)) and inositol-1,3,4,5-tetrakisphosphate (InsP(4)) receptors have been located to the nucleus and their role in nuclear calcium signaling has been proposed, Outer nuclear membrane was separated from the inner membrane. The two membrane preparations were, as best as possible, devoid of cross contamination as attested by marker enzyme activity, Western blotting with antilamin antibody, and electron microscopy, InsP(4) receptor and Ca2+-ATPase were located to the outer nuclear membrane. InsP(3) receptor was located to the inner nuclear membrane. ATP or InsP(4) induced nuclear calcium uptake, External free calcium concentration, in the medium bathing the nuclei, determined the choice for ATP or InsP(4)-mediated calcium transport. We present a mechanistic model for nuclear calcium transport. According to this model, calcium can reach the nucleus envelope either by the action of ATP or InsP(4). However, the calcium release from the nucleus envelope to the nucleoplasm is mediated by InsP(3) through the activation of InsP(3) receptor, which is located to the inner nuclear membrane. The action of InsP(3) in this process was instantaneous and transient and was sensitive to heparin.