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MAL/VIP17，肾脏中 NKCC2 调节的新成员。

MAL/VIP17, a new player in the regulation of NKCC2 in the kidney.

机构信息

Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06511, USA.

出版信息

Mol Biol Cell. 2010 Nov 15;21(22):3985-97. doi: 10.1091/mbc.E10-05-0456. Epub 2010 Sep 22.

DOI:10.1091/mbc.E10-05-0456
PMID:20861303
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2982131/
Abstract

The renal-specific Na+-K+-2Cl- cotransporter (NKCC2) is the major salt transport pathway of the apical membrane of the mammalian thick ascending limb of Henle's loop. Here, we analyze the role of the tetraspan protein myelin and lymphocytes-associated protein (MAL)/VIP17 in the regulation of NKCC2. We demonstrated that 1) NKCC2 and MAL/VIP17 colocalize and coimmunoprecipitate in Lilly Laboratories cell porcine kidney cells (LLC-PK1) as well as in rat kidney medullae, 2) a 150-amino acid stretch of NKCC2 C-terminal tail is involved in the interaction with MAL/VIP17, 3) MAL/VIP17 increases the cell surface retention of NKCC2 by attenuating its internalization, and 4) this coincides with an increase in cotransporter phosphorylation. Interestingly, overexpression of MAL/VIP17 in the kidney of transgenic mice results in cysts formation in distal nephron structures consistent with the hypothesis that MAL/VIP17 plays an important role in apical sorting or in maintaining the stability of the apical membrane. The NKCC2 expressed in these mice was highly glycosylated and phosphorylated, suggesting that MAL/VIP17 also is involved in the stabilization of NKCC2 at the apical membrane in vivo. Thus, the involvement of MAL/VIP17 in the activation and surface expression of NKCC2 could play an important role in the regulated absorption of Na+ and Cl- in the kidney.

摘要

肾脏特异性钠钾 2 氯协同转运蛋白（NKCC2）是哺乳动物亨利氏袢升支粗段顶端膜的主要盐转运途径。在这里，我们分析了四跨膜蛋白髓鞘和淋巴细胞相关蛋白（MAL）/VIP17 在调节 NKCC2 中的作用。我们证明了 1）NKCC2 和 MAL/VIP17 在 Lilly 实验室猪肾细胞（LLC-PK1）以及大鼠肾脏髓质中共定位和共免疫沉淀，2）NKCC2 C 末端尾部的 150 个氨基酸延伸与 MAL/VIP17 相互作用，3）MAL/VIP17 通过减弱 NKCC2 的内化来增加 NKCC2 的细胞表面保留，4）这与协同转运蛋白磷酸化增加相一致。有趣的是，在转基因小鼠肾脏中过表达 MAL/VIP17 会导致远端肾单位结构中的囊肿形成，这与 MAL/VIP17 在顶端分拣或维持顶端膜稳定性方面发挥重要作用的假设一致。在这些小鼠中表达的 NKCC2 高度糖基化和磷酸化，表明 MAL/VIP17 也参与了 NKCC2 在体内顶端膜的稳定。因此，MAL/VIP17 参与 NKCC2 的激活和表面表达可能在肾脏中对 Na+和 Cl-的调节吸收中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/b316d744af4e/zmk0221096460007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/9e83a781ba9c/zmk0221096460001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/d4c018fd0a8c/zmk0221096460002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/29258e59453d/zmk0221096460003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/7ea0cfdab24d/zmk0221096460004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/87d818eacd62/zmk0221096460005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/4835e554bf80/zmk0221096460006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/b316d744af4e/zmk0221096460007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/9e83a781ba9c/zmk0221096460001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/d4c018fd0a8c/zmk0221096460002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/29258e59453d/zmk0221096460003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/7ea0cfdab24d/zmk0221096460004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/87d818eacd62/zmk0221096460005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/4835e554bf80/zmk0221096460006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce3/2982131/b316d744af4e/zmk0221096460007.jpg

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