Quantitative proteomics reveals TMOD1-related proteins associated with water balance regulation
Quantitative proteomics reveals TMOD1-related proteins associated with water balance regulation
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定量蛋白质组学揭示与水平衡调节相关的 TMOD1 相关蛋白
DOI：
10.1371/journal.pone.0219932
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发表时间：
2019-07
期刊：
影响因子：
3.7
通讯作者：
Yao Weijuan
中科院分区：
文献类型：
--
作者：
Wang Wenjun;Xu Dingwen;Zhong Lijun;Zhang Wenxi;Kang Jihong;Zhou Jing;Ka Weibo;Sun Dagong;Xia Xue;Xie Lide;Yao Weijuan
肾脏中的远端小管和集合管调节水平衡。TMOD 1是一种肌动蛋白加帽蛋白，在控制肌动蛋白丝的组织中起重要作用。本研究发现TMOD 1在远端小管和集合管中特异性表达。为了研究TMOD 1的作用，我们创建了Tmod 1flox/flox小鼠，并将其与Ksp-Cre小鼠进行繁殖，以产生小管特异性Tmod 1敲除小鼠，Tmod 1flox/flox/Ksp-Cre+（命名为TFK）。与对照组小鼠相比，TFK小鼠出现少尿、高渗尿和高血压。为了确定这种表型的机制，我们对TFK和对照小鼠的肾脏进行了无标记定量蛋白质组学研究。共发现83个差异表达蛋白。生物信息学分析表明，TMOD 1调控网络涉及蛋白质磷酸化和代谢等生物学过程。基因集富集分析表明，多种途径，如磷脂酰肌醇信号系统和GnRH信号通路，与Tmod 1基因敲除密切相关。Western blot证实了TFK小鼠肾脏中TGFBR 2、SLC 25 A11和MTFP 1三种蛋白的下调。本研究为深入了解Tmod 1基因在肾脏中的分子功能、调控网络以及水平衡调控的新机制提供了有价值的信息。
The distal tubule and collecting duct in kidney regulate water homeostasis. TMOD1 is an actin capping protein that plays an important role in controlling the organization of actin filaments. In this study, we found TMOD1 was specifically expressed in distal tubules and collecting ducts. To investigate the role of TMOD1, we created Tmod1flox/flox mice and bred them with Ksp-Cre mice to generate tubule-specific Tmod1 knockout mice, Tmod1flox/flox/Ksp-Cre+ (designated as TFK). As compared with control mice, TFK mice showed oliguria, hyperosmolality urine, and high blood pressure. To determine the mechanisms underlying this phenotype, we performed label-free quantitative proteomics on kidneys of TFK and control mice. Total of 83 proteins were found differentially expressed. Bioinformatic analysis indicated that biological processes, including protein phosphorylation and metabolic process, were involved in TMOD1 regulatory network. Gene set enrichment analysis showed that multiple pathways, such as phosphatidylinositol signaling system and GnRH signaling pathway, were strongly associated with Tmod1 knockout. Western blot validated the down-regulation of three proteins, TGFBR2, SLC25A11, and MTFP1, in kidneys of TFK mice. Our study provides valuable information on the molecular functions and the regulatory network of Tmod1 gene in kidney, as well as the new mechanisms for the regulation of water balance.
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影响因子：
2.8
作者：
T. Green;C. Vera;Mark A Sussman;M. Martone;L. Sung
通讯作者：
T. Green;C. Vera;Mark A Sussman;M. Martone;L. Sung
DOI：
10.1152/ajprenal.00336.2016
发表时间：
2016-10
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Fahmy A. Mamuya;José Luis Cano-Peñalver;Wei Li;D. Rodríguez Puyol;M. Rodriguez Puyol;Dennis Brown;S. de Frutos;H. Lu
通讯作者：
Fahmy A. Mamuya;José Luis Cano-Peñalver;Wei Li;D. Rodríguez Puyol;M. Rodriguez Puyol;Dennis Brown;S. de Frutos;H. Lu
DOI：
10.1016/s0021-9258(18)45276-3
发表时间：
1987-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
V. Fowler
通讯作者：
V. Fowler
mTORC1 通路中 RagA GTPase 突变与常染色体显性白内障相关
影响因子：
4.5
作者：
Chen JH;Huang C;Zhang B;Yin S;Liang J;Xu C;Huang Y;Cen LP;Ng TK;Zheng C;Zhang S;Chen H;Pang CP;Zhang M
通讯作者：
Zhang M
定量蛋白质组学揭示 EVA1A 相关蛋白参与神经元分化
影响因子：
3.4
作者：
Zhong L;Zhou J;Chen X;Liu J;Liu Z;Chen Y;Bai Y
通讯作者：
Bai Y