清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Rac1 Suppression by the Focal Adhesion Protein GIT ArfGAP2 and Podocyte Protection

基因敲除 RAC1 足细胞 PTK2 焦点粘着 适配器分子crk 原钙粘蛋白 细胞生物学 细胞粘附 酪氨酸 肌动蛋白细胞骨架 生物 细胞骨架 钙粘蛋白 磷酸化 生物化学 信号转导衔接蛋白 信号转导 内分泌学 细胞 蛋白激酶A 基因 丝裂原活化蛋白激酶激酶 蛋白尿
作者
Naoyuki Shimada,Jun Matsuda,Kana Asano-Matsuda,Maho Tokuchi,Lamine Aoudjit,Agnieszka Masztalerz,Serge Lemay,Tomoko Takano,Yoshitaka Isaka
出处
期刊:Journal of The American Society of Nephrology [American Society of Nephrology]
卷期号:36 (6): 1088-1104 被引量:2
标识
DOI:10.1681/asn.0000000614
摘要

Key Points Focal adhesion protein GIT2 protected podocytes from injury in rodent proteinuric disease models. GIT2 facilitated translocation of tyrosine phosphatase PTP1B to focal adhesions where it dephosphorylates p130Cas, thereby suppressing Rac1 activity. Stabilizing GIT2 or facilitating GIT2 localization to focal adhesions in podocytes could be a therapeutic strategy in proteinuric kidney diseases. Background Podocytes have an intricate structure featured by numerous actin-based projections called foot processes. Rho family of small GTPases, including Ras-related C3 botulinum toxin substrate 1 (Rac1), play important roles in actin cytoskeletal remodeling required for cell morphology and adhesion. We previously showed that Rac1 activation in podocytes causes foot process effacement and proteinuria, but the upstream and spatiotemporal regulatory mechanism directing Rac1 is largely unknown. Recently, we identified the focal adhesion protein GIT ArfGAP2 (GIT2) as one of the Rac1 interactors in human podocytes by proximity-dependent biotin identification and proteomics. Methods Systemic and podocyte-specific GIT2 knockout mice were generated and assessed for kidney phenotypes. Human podocytes with GIT2 knockdown (KD) and overexpression were established using lentiviral transduction and characterized. Results GIT2 was enriched in glomeruli, including podocytes, in the mouse kidney. Gene deletion of Git2 in podocytes caused exacerbated proteinuria and foot process effacement when subjected to the minimal change disease model and salt-sensitive hypertension model, which were improved by pharmacological inhibition of Rac1. In cultured podocytes, GIT2 KD resulted in Rac1-dependent cell spreading with marked lamellipodial protrusions, accelerated focal adhesion disassembly, and shorter focal adhesion lifetime. In GIT2 KD podocytes, tyrosine phosphorylation of the focal adhesion protein p130 Crk-associated substrate (Cas) was significantly increased, accompanied by impaired localization of the tyrosine phosphatase PTP1B to focal adhesions. These phenotypes observed in GIT2 KD podocytes were reversed by GIT2 overexpression. Conclusions The results indicate that GIT2 facilitates translocation of PTP1B to focal adhesions where it dephosphorylates p130Cas, thereby suppressing local Rac1 activity and protecting against podocyte injury and proteinuria.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
不安的如天完成签到,获得积分10
20秒前
Kao应助科研通管家采纳,获得10
20秒前
Kao应助科研通管家采纳,获得10
20秒前
Kao应助科研通管家采纳,获得10
20秒前
木昆完成签到 ,获得积分10
32秒前
大个应助木昆采纳,获得10
44秒前
研友_8Y2DXL完成签到,获得积分10
48秒前
欣喜的涵柏完成签到 ,获得积分10
52秒前
77wlr完成签到,获得积分10
53秒前
xiang完成签到,获得积分10
59秒前
wakawaka完成签到 ,获得积分10
59秒前
Akim应助聪明怜阳采纳,获得10
59秒前
1分钟前
优秀的流沙完成签到,获得积分10
1分钟前
1分钟前
xiaowangwang完成签到 ,获得积分10
1分钟前
木昆发布了新的文献求助10
1分钟前
粗暴的镜子完成签到,获得积分10
1分钟前
聪明怜阳发布了新的文献求助10
1分钟前
小鸭嘎嘎完成签到 ,获得积分10
1分钟前
聪明怜阳完成签到,获得积分10
1分钟前
耍酷的指甲油完成签到 ,获得积分10
1分钟前
务实的一斩完成签到 ,获得积分10
1分钟前
彩色的芷容完成签到 ,获得积分20
1分钟前
changfox完成签到,获得积分10
1分钟前
迅速的千风完成签到 ,获得积分10
1分钟前
fyj完成签到 ,获得积分10
1分钟前
大大大忽悠完成签到 ,获得积分10
1分钟前
always完成签到,获得积分10
1分钟前
zl完成签到,获得积分10
1分钟前
冷静的尔竹完成签到,获得积分10
2分钟前
Axel完成签到,获得积分10
2分钟前
淡然的冬瓜完成签到,获得积分10
2分钟前
muriel完成签到,获得积分0
2分钟前
creep2020完成签到,获得积分0
2分钟前
e746700020完成签到,获得积分10
2分钟前
Kao应助科研通管家采纳,获得10
2分钟前
Kao应助科研通管家采纳,获得10
2分钟前
2分钟前
忘忧Aquarius完成签到,获得积分0
2分钟前
高分求助中
Principles of Economics, 11th Edition 10000
University Physics with Modern Physics, 16th edition 10000
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
Development of a Bridge Weigh-In-Motion System: A technology to convert the bridge response to the passage of traffic into data on vehicle configurations, speeds, times of travel and weights 1000
ズームレンズの光学設計に関する研究 800
Fundamentals of Pharmaceutical and Biologics Regulations: A Global Perspective, Second Edition 700
Matrix Methods in Data Mining and Pattern Recognition Second Edition 610
热门求助领域 (近24小时)
化学 材料科学 医学 生物 纳米技术 工程类 有机化学 化学工程 生物化学 计算机科学 内科学 物理 复合材料 催化作用 细胞生物学 无机化学 光电子学 物理化学 电极 基因
热门帖子
关注 科研通微信公众号,转发送积分 7282125
求助须知:如何正确求助?哪些是违规求助? 8902995
关于积分的说明 18833740
捐赠科研通 6953175
什么是DOI,文献DOI怎么找? 3207556
关于科研通互助平台的介绍 2377826
邀请新用户注册赠送积分活动 2182729