Expression of RASSF6 in kidney and the implication of RASSF6 and the Hippo pathway in the sorbitol-induced apoptosis in renal proximal tubular epithelial cells.
Expression of RASSF6 in kidney and the implication of RASSF6 and the Hippo pathway in the sorbitol-induced apoptosis in renal proximal tubular epithelial cells.
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DOI：
10.1093/jb/mvs056
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发表时间：
2012-07
影响因子：
2.7
通讯作者：
Kanchanamala Withanage;K. Nakagawa;Mitsunobu Ikeda;H. Kurihara;Takumi Kudo;Zeyu Yang;A. Sakane;Takuya Sasaki;Y. Hata
中科院分区：
文献类型：
--
作者：
Kanchanamala Withanage;K. Nakagawa;Mitsunobu Ikeda;H. Kurihara;Takumi Kudo;Zeyu Yang;A. Sakane;Takuya Sasaki;Y. Hata
RASSF 6是RASSF肿瘤抑制蛋白的一个成员，与哺乳动物Ste 20样激酶（MST 1/2）结合，MST 1/2是促凋亡Hippo通路的核心激酶，并与Hippo通路合作诱导凋亡。我们最初通过酵母双杂交筛选将RASSF 6鉴定为膜相关鸟苷酸激酶反向（MAGI）-1的假定相互作用物。我们利用人肾cDNA文库进行筛选。MAGI-1在肾脏中大量表达，是裂膈的核心成分。这些发现表明RASSF 6在肾脏中表达。然而，RASSF 6在肾脏中的功能尚未研究。本研究旨在证实RASSF 6与MAGI-1的相互作用，分析RASSF 6在肾脏中的表达，并深入了解RASSF 6在肾脏中的功能。RASSF 6通过其C末端PDZ结合基序与MAGI-1的PDZ结构域结合，并与来自大鼠肝脏的MAGI-1共免疫沉淀。RASSF 6定位于正常肾小球中，但在肾病肾中当裂隙隔膜被破坏时消失。RASSF 6也定位于肾近端小管上皮细胞的顶膜上。我们证明RASSF 6以及Hippo通路参与了在永生化人近端肾小管上皮HK-2细胞中的胆固醇诱导的凋亡。
RASSF6, a member of RASSF tumour suppressor proteins, binds to mammalian Ste20-like kinases (MST1/2), core kinases of the proapoptotic Hippo pathway and cooperates with the Hippo pathway to induce apoptosis. We originally identified RASSF6 as a putative interactor of membrane-associated guanylate kinase inverted (MAGI)-1 by the yeast two-hybrid screening. We used human kidney cDNA library for the screening. MAGI-1 is abundantly expressed in kidney and is a core component of the slit diaphragm. These findings suggest that RASSF6 is expressed in kidney. However, the function of RASSF6 in kidney is not yet studied. We performed this study to confirm the interaction of RASSF6 with MAGI-1, to analyse the expression of RASSF6 in kidney and to gain insight into the function of RASSF6 in kidney. RASSF6 binds to PDZ domains of MAGI-1 through its C-terminal PDZ-binding motif and is coimmunoprecipitated with MAGI-1 from rat liver. RASSF6 is localized in normal kidney glomerulus but disappears when the slit diaphragm is disrupted in nephrotic kidney. RASSF6 is also localized on apical membranes in renal proximal tubular epithelial cells. We demonstrated that RASSF6 as well as the Hippo pathway are involved in the sorbitol-induced apoptosis in immortalized human proximal renal tubular epithelial HK-2 cells.