IQGAP1 regulates actin cytoskeleton organization in podocytes through interaction with nephrin.
IQGAP1 regulates actin cytoskeleton organization in podocytes through interaction with nephrin.
复制标题
IQGAP1通过与肾素的相互作用来调节足细胞中肌动蛋白细胞骨架组织。
DOI：
10.1016/j.cellsig.2015.01.015
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发表时间：
2015-04
影响因子：
4.8
通讯作者：
Ding G
中科院分区：
文献类型：
--
作者：
Liu Y;Liang W;Yang Y;Pan Y;Yang Q;Chen X;Singhal PC;Ding G
越来越多的数据表明，足细胞的细胞骨架重组参与蛋白尿的发生和肾小球疾病的进展。去氧肾上腺素充当狭缝隔膜的信号传感器，传递细胞骨架信号以维持足细胞的独特结构。然而，去氧肾上腺素信号级联反应值得进一步研究。 IQGAP1 是一种支架蛋白，能够调节细胞骨架组织。据推测，IQGAP1 通过与去氧肾上腺素相互作用，有助于足细胞中肌动蛋白的重组。注射嘌呤霉素氨基核苷的大鼠肾小球中 IQGAP1 表达和 IQGAP1-nephrin 共定位逐渐降低，然后逐渐恢复，与足突融合和蛋白尿的发展一致。在培养的人足细胞中，IQGAP1 siRNA 加剧了嘌呤霉素氨基核苷诱导的 F-肌动蛋白破坏以及迁移和扩散紊乱，而野生型 IQGAP1 质粒可部分恢复这些影响。此外，通过野生型 IQGAP1 和去氧肾上腺素质粒共转染，COS7 细胞中细胞松弛素 D 刺激的细胞骨架紊乱得以恢复，但通过野生型 IQGAP1 质粒的单转染或突变型 IQGAP1 [Δ1443(S → A)] 和共转染都无法恢复。 野生型去氧肾上腺素质粒。使用过表达去氧肾上腺素和 IQGAP1 的每个衍生结构域分子的 COS7 细胞裂解物进行的免疫共沉淀分析表明，IQGAP1 羧基末端的聚脯氨酸结合结构域和 RasGAP 结构域是与去氧肾上腺素相互作用的靶模块。总的来说，这些发现表明，激活的 IQGAP1 作为去氧肾上腺素的细胞内伴侣，参与肌动蛋白细胞骨架的组织和足细胞的功能调节。
Increasing data has shown that the cytoskeletal reorganization of podocytes is involved in the onset of proteinuria and the progression of glomerular disease. Nephrin behaves as a signal sensor of the slit diaphragm to transmit cytoskeletal signals to maintain the unique structure of podocytes. However, the nephrin signaling cascade deserves further study. IQGAP1 is a scaffolding protein with the ability to regulate cytoskeletal organization. It is hypothesized that IQGAP1 contributes to actin reorganization in podocytes through interaction with nephrin. IQGAP1 expression and IQGAP1-nephrin colocalization in glomeruli were progressively decreased and then gradually recovered in line with the development of foot process fusion and proteinuria in puromycin aminonucleoside-injected rats. In cultured human podocytes, puromycin aminonucleoside-induced disruption of F-actin and disorders of migration and spreading were aggravated by IQGAP1 siRNA, and these effects were partially restored by a wild-type IQGAP1 plasmid. Furthermore, the cytoskeletal disorganization stimulated by cytochalasin D in COS7 cells was recovered by cotransfection with wild-type IQGAP1 and nephrin plasmids but was not recovered either by single transfection of the wild-type IQGAP1 plasmid or by cotransfection of mutant IQGAP1 [Δ1443(S → A)] and wild-type nephrin plasmids. Co-immunoprecipitation analysis using lysates of COS7 cells overexpressing nephrin and each derivative-domain molecule of IQGAP1 demonstrated that the poly-proline binding domain and RasGAP domain in the carboxyl terminus of IQGAP1 are the target modules that interact with nephrin. Collectively, these findings showed that activated IQGAP1, as an intracellular partner of nephrin, is involved in actin cytoskeleton organization and functional regulation of podocytes.
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影响因子：
18.2
作者：
Greka A;Mundel P
通讯作者：
Mundel P
影响因子：
4.8
作者：
Reiser, J;Oh, J;Mundel, P
通讯作者：
Mundel, P
影响因子：
15.9
作者：
Daehn, Ilse;Casalena, Gabriella;Bottinger, Erwin P.
通讯作者：
Bottinger, Erwin P.
DOI：
10.1073/pnas.0504166102
发表时间：
2005-07-12
影响因子：
11.1
作者：
Lehtonen, S;Ryan, JJ;Farquhar, MG
通讯作者：
Farquhar, MG
DOI：
10.3181/00379727-142-36977
发表时间：
1973-01-01
影响因子：
--
作者：
BURLINGTON, H;CRONKITE, EP
通讯作者：
CRONKITE, EP