Intracellular pH regulation by Na(+)/H(+) exchange requires phosphatidylinositol 4,5-bisphosphate.
Intracellular pH regulation by Na(+)/H(+) exchange requires phosphatidylinositol 4,5-bisphosphate.
复制标题
Na（+）/H（+）交换的细胞内pH调节需要磷脂酰肌醇4,5-双磷酸。
DOI：
10.1083/jcb.150.1.213
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发表时间：
2000-07-10
期刊：
影响因子：
--
通讯作者：
Grinstein S
中科院分区：
文献类型：
--
作者：
Aharonovitz O;Zaun HC;Balla T;York JD;Orlowski J;Grinstein S
载体介导的跨质膜Na+到H+的电子中和交换并不直接消耗代谢能量。然而，细胞内ATP的急性耗尽显著地减少了转运。我们分析了多磷肌醇可能参与了NHE1的代谢调节，NHE1是Na+/H+交换器的普遍存在的异构体。ATP耗竭伴随着血浆磷脂酰肌醇4，5-二磷酸(PIP2)含量的显著降低。此外，在没有ATP耗竭的情况下，血浆膜PIP2的隔离或水解与NHE1活性的严重抑制有关。对NHE1 COOH末端结构域的一级结构的研究发现了两个潜在的PIP2结合基序。编码这些基序的融合蛋白在体外与PIP2结合。当NHE1基因被导入到抗端口缺陷细胞中时，缺失PIP2结合域的突变型NHE1的转运能力大大降低，这意味着需要与PIP2结合才能获得最佳活性。这些发现表明，NHE1的活性受磷脂酰肌醇的调节，ATP耗竭的抑制作用可能至少部分归因于伴随的PIP2的净去磷酸化。
The carrier-mediated, electroneutral exchange of Na+ for H+ across the plasma membrane does not directly consume metabolic energy. Nevertheless, acute depletion of cellular ATP markedly decreases transport. We analyzed the possible involvement of polyphosphoinositides in the metabolic regulation of NHE1, the ubiquitous isoform of the Na+/H+ exchanger. Depletion of ATP was accompanied by a marked reduction of plasmalemmal phosphatidylinositol 4,5-bisphosphate (PIP2) content. Moreover, sequestration or hydrolysis of plasmalemmal PIP2, in the absence of ATP depletion, was associated with profound inhibition of NHE1 activity. Examination of the primary structure of the COOH-terminal domain of NHE1 revealed two potential PIP2-binding motifs. Fusion proteins encoding these motifs bound PIP2 in vitro. When transfected into antiport-deficient cells, mutant forms of NHE1 lacking the putative PIP2-binding domains had greatly reduced transport capability, implying that association with PIP2 is required for optimal activity. These findings suggest that NHE1 activity is modulated by phosphoinositides and that the inhibitory effect of ATP depletion may be attributable, at least in part, to the accompanying net dephosphorylation of PIP2.
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影响因子：
56.9
作者：
Baukrowitz, T;Schulte, U;Fakler, B
通讯作者：
Fakler, B
DOI：
10.1073/pnas.92.23.10472
发表时间：
1995-11-07
影响因子：
11.1
作者：
LEMMON, MA;FERGUSON, KM;SCHLESSINGER, J
通讯作者：
SCHLESSINGER, J
影响因子：
--
作者：
Aharonovitz, O;Grinstein, S
通讯作者：
Grinstein, S
DOI：
10.1152/ajpcell.1998.275.4.c1158
发表时间：
1998-10-01
影响因子：
5.5
作者：
Gan, BS;Krump, E;Grinstein, S
通讯作者：
Grinstein, S
DOI：
10.1073/pnas.93.22.12631
发表时间：
1996-10-29
影响因子：
11.1
作者：
Lin, X;Barber, DL
通讯作者：
Barber, DL