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Rab 蛋白:对子宫内膜细胞内运输的深入了解。

Rab Proteins: Insights into Intracellular Trafficking in Endometrium.

机构信息

CONICET-UNCuyo-IMBECU, 5500, Mendoza, Argentina.

Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, 5500, Mendoza, Argentina.

出版信息

Reprod Sci. 2021 Jan;28(1):12-22. doi: 10.1007/s43032-020-00256-w. Epub 2020 Jul 7.

DOI:10.1007/s43032-020-00256-w
PMID:32638281
Abstract

Rab proteins belong to the Ras superfamily of small monomeric GTPases. These G proteins are the main controllers of vesicular transport in every tissue, among them, the endometrium. They are in charge of to the functional subcellular compartmentalization and cargo transport between organelles and the plasma membrane. In turn, intracellular trafficking contributes to endometrial changes during the menstrual cycle, secretion to the uterine fluid, and trophoblast implantation; however, few reports analyze the role of Rab proteins in the uterus. In general, Rab proteins control the release of cytokines, growth factors, enzymes, hormones, cell adhesion molecules, and mucus. Further, the secretion of multiple compounds into the uterine cavity is required for successful implantation. Therefore, alterations in Rab-controlled intracellular transport likely impair secretory processes to the uterine fluid that may correlate with abnormal endometrial development and failed reproductive outcomes. Overall, they could explain recurrent miscarriages, female infertility, and/or assisted reproductive failure. Interestingly, estrogen (E2) and progesterone (P) regulate gene expression of Rab proteins involved in secretory pathways. This review aims to gather information regarding the role of Rab proteins and intracellular trafficking in the endometrium during the different menstrual phases, and in the generation of a receptive stage for embryo implantation, modulated by E2 and P. This knowledge might be useful for the development of novel reproductive therapies that overcome low implantation rates of assisted reproductive procedures.

摘要

Rab 蛋白属于 Ras 超家族的小单体 GTP 酶。这些 G 蛋白是每种组织中囊泡运输的主要控制器,其中包括子宫内膜。它们负责功能性亚细胞区室化和细胞器与质膜之间的货物运输。反过来,细胞内运输有助于月经周期中子宫内膜的变化、分泌到子宫液中以及滋养层植入;然而,很少有报道分析 Rab 蛋白在子宫中的作用。一般来说,Rab 蛋白控制细胞因子、生长因子、酶、激素、细胞粘附分子和粘液的释放。此外,需要将多种化合物分泌到子宫腔中才能成功植入。因此,Rab 控制的细胞内运输的改变可能会破坏对子宫液的分泌过程,这可能与异常的子宫内膜发育和生殖失败有关。总的来说,它们可以解释反复流产、女性不孕和/或辅助生殖失败。有趣的是,雌激素 (E2) 和孕激素 (P) 调节参与分泌途径的 Rab 蛋白的基因表达。本综述旨在收集有关 Rab 蛋白和细胞内运输在不同月经阶段的子宫内膜中的作用的信息,以及在胚胎植入的接受阶段的产生,由 E2 和 P 调节。这些知识可能对开发新的生殖治疗方法有用,这些方法可以克服辅助生殖程序中低植入率的问题。

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The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling.Rab 效应蛋白 RABEP2 调节内体运输,从而介导血管内皮生长因子受体-2(VEGFR2)依赖性信号转导。
J Biol Chem. 2018 Mar 30;293(13):4805-4817. doi: 10.1074/jbc.M117.812172. Epub 2018 Feb 7.
2
17β-Estradiol inhibits estrogen binding protein-mediated hypha formation in Candida albicans.17β-雌二醇抑制雌激素结合蛋白介导的白色念珠菌菌丝形成。
Microb Pathog. 2017 Aug;109:151-155. doi: 10.1016/j.micpath.2017.05.038. Epub 2017 May 25.
3
Involvement of ARHGEF10, GEF for RhoA, in Rab6/Rab8-mediating membrane traffic.
RhoA鸟嘌呤核苷酸交换因子ARHGEF10参与Rab6/Rab8介导的膜运输。
Small GTPases. 2019 May;10(3):169-177. doi: 10.1080/21541248.2017.1302550. Epub 2017 Apr 27.
4
Rab GTPases: master regulators that establish the secretory and endocytic pathways.Rab GTP酶:建立分泌途径和内吞途径的主要调节因子。
Mol Biol Cell. 2017 Mar 15;28(6):712-715. doi: 10.1091/mbc.E16-10-0737.
5
New insights into the function of Rab GTPases in the context of exosomal secretion.关于Rab GTPases在外泌体分泌过程中的功能的新见解。
Small GTPases. 2018 Mar 4;9(1-2):95-106. doi: 10.1080/21541248.2016.1264352. Epub 2017 Jan 31.
6
RAB39a binds caspase-1 and is required for caspase-1-dependent interleukin-1β secretion.RAB39a与半胱天冬酶-1结合,是半胱天冬酶-1依赖性白细胞介素-1β分泌所必需的。
J Biol Chem. 2016 Nov 18;291(47):24800. doi: 10.1074/jbc.A109.046102.
7
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Biol Reprod. 2016 Nov;95(5):109. doi: 10.1095/biolreprod.116.143503. Epub 2016 Sep 21.
8
Fertile ground: human endometrial programming and lessons in health and disease.肥沃的土壤:人类子宫内膜编程与健康和疾病的相关课程。
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