当前位置: X-MOL 学术J. Appl. Physiol. Cell Physiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
WNK3 and WNK4 exhibit opposite sensitivity with respect to cell volume and intracellular chloride concentration.
American Journal of Physiology-Cell Physiology ( IF 5.0 ) Pub Date : 2020-07-28 , DOI: 10.1152/ajpcell.00488.2019
Diana Pacheco-Alvarez 1 , Diego Luis Carrillo-Pérez 2, 3 , Adriana Mercado 4 , Karla Leyva-Ríos 1 , Erika Moreno 5 , Elisa Hernández-Mercado 1 , María Castañeda-Bueno 5 , Norma Vázquez 6 , Gerardo Gamba 3, 5, 6
Affiliation  

Cation-coupled chloride cotransporters (CCC) play a role in modulating intracellular chloride concentration ([Cl]i) and cell volume. Cell shrinkage and cell swelling are accompanied by an increase or decrease in [Cl]i, respectively. Cell shrinkage and a decrease in [Cl]i increase the activity of NKCCs (Na-K-Cl cotransporters: NKCC1, NKCC2, and Na-Cl) and inhibit the activity of KCCs (K-Cl cotransporters: KCC1 to KCC4), wheras cell swelling and an increase in [Cl]i activate KCCs and inhibit NKCCs; thus, it is unlikely that the same kinase is responsible for both effects. WNK1 and WNK4 are chloride-sensitive kinases that modulate the activity of CCC in response to changes in [Cl]i. Here, we showed that WNK3, another member of the serine-threonine kinase WNK family with known effects on CCC, is not sensitive to [Cl]i but can be regulated by changes in extracellular tonicity. In contrast, WNK4 is highly sensitive to [Cl]i but is not regulated by changes in cell volume. The activity of WNK3 toward NaCl cotransporter is not affected by eliminating the chloride-binding site of WNK3, further confirming that the kinase is not sensitive to chloride. Chimeric WNK3/WNK4 proteins were produced, and analysis of the chimeras suggests that sequences within the WNK’s carboxy-terminal end may modulate the chloride affinity. We propose that WNK3 is a cell volume-sensitive kinase that translates changes in cell volume into phosphorylation of CCC.

中文翻译:

WNK3 和 WNK4 对细胞体积和细胞内氯化物浓度表现出相反的敏感性。

阳离子偶联氯离子协同转运蛋白 (CCC) 在调节细胞内氯离子浓度 ([Cl - ] i ) 和细胞体积方面发挥作用。细胞收缩和细胞膨胀分别伴随着[Cl - ] i的增加或减少。细胞收缩和在下降[氯- ]增加NKCCs(钠-K-CL协同转运蛋白:NKCC1,NKCC2,和Na-Cl)的活性和抑制的KCC的活性(K-CL协同转运蛋白:KCC1到KCC4),鉴于细胞肿胀和 [Cl - ] i 增加激活 KCCs 并抑制 NKCCs;因此,同一种激酶不太可能导致这两种效应。WNK1 和 WNK4 是氯敏感激酶,可响应 [Cl - ] i 的变化调节 CCC 的活性。在这里,我们表明 WNK3,丝氨酸 - 苏氨酸激酶 WNK 家族的另一个成员,对 CCC 具有已知的影响,对 [Cl - ] i不敏感,但可以通过细胞外张力的变化进行调节。相比之下,WNK4 对 [Cl - ] i高度敏感但不受细胞体积变化的调节。WNK3 对 NaCl 协同转运蛋白的活性不受消除 WNK3 的氯化物结合位点的影响,进一步证实该激酶对氯化物不敏感。产生了嵌合 WNK3/WNK4 蛋白,对嵌合体的分析表明 WNK 羧基末端内的序列可能会调节氯化物亲和力。我们提出 WNK3 是一种细胞体积敏感激酶,可将细胞体积的变化转化为 CCC 的磷酸化。
更新日期:2020-08-20
down
wechat
bug