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Rho GTPases 作为肠道黏膜和胃肠道疾病中的关键分子参与者。

Rho GTPases as Key Molecular Players within Intestinal Mucosa and GI Diseases.

机构信息

Department of Medicine 1, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.

出版信息

Cells. 2021 Jan 4;10(1):66. doi: 10.3390/cells10010066.

Abstract

Rho proteins operate as key regulators of the cytoskeleton, cell morphology and trafficking. Acting as molecular switches, the function of Rho GTPases is determined by guanosine triphosphate (GTP)/guanosine diphosphate (GDP) exchange and their lipidation via prenylation, allowing their binding to cellular membranes and the interaction with downstream effector proteins in close proximity to the membrane. A plethora of in vitro studies demonstrate the indispensable function of Rho proteins for cytoskeleton dynamics within different cell types. However, only in the last decades we have got access to genetically modified mouse models to decipher the intricate regulation between members of the Rho family within specific cell types in the complex in vivo situation. Translationally, alterations of the expression and/or function of Rho GTPases have been associated with several pathological conditions, such as inflammation and cancer. In the context of the GI tract, the continuous crosstalk between the host and the intestinal microbiota requires a tight regulation of the complex interaction between cellular components within the intestinal tissue. Recent studies demonstrate that Rho GTPases play important roles for the maintenance of tissue homeostasis in the gut. We will summarize the current knowledge on Rho protein function within individual cell types in the intestinal mucosa in vivo, with special focus on intestinal epithelial cells and T cells.

摘要

Rho 蛋白作为细胞骨架、细胞形态和运输的关键调节剂发挥作用。作为分子开关,Rho GTP 酶的功能取决于鸟嘌呤三磷酸(GTP)/鸟嘌呤二磷酸(GDP)交换及其通过prenylation 的脂化,允许它们与细胞膜结合,并与靠近膜的下游效应蛋白相互作用。大量的体外研究表明,Rho 蛋白对于不同细胞类型中的细胞骨架动力学具有不可或缺的功能。然而,只有在过去几十年中,我们才获得了基因修饰的小鼠模型,以在复杂的体内情况下破译特定细胞类型中 Rho 家族成员之间的复杂调节。在翻译水平上,Rho GTP 酶的表达和/或功能的改变与几种病理状况有关,如炎症和癌症。在胃肠道的背景下,宿主和肠道微生物群之间的持续串扰需要对肠道组织中细胞成分之间的复杂相互作用进行严格调节。最近的研究表明,Rho GTP 酶在维持肠道组织稳态方面发挥着重要作用。我们将总结 Rho 蛋白在体内肠道黏膜中单个细胞类型中的功能的最新知识,特别关注肠上皮细胞和 T 细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/073b/7823293/8ea5d77f6066/cells-10-00066-g001.jpg

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