Shibata Satoshi, Teshima Yui, Niimi Kenta, Inagaki Shinobu
a Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine , Osaka University , Osaka , Japan.
Small GTPases. 2019 May;10(3):169-177. doi: 10.1080/21541248.2017.1302550. Epub 2017 Apr 27.
Small GTPases play crucial roles in the maintenance of a homeostatic environment and appropriate movements of the cell. In these processes, the direct or indirect interaction between distinct small GTPases could be required for regulating mutual signaling pathways. In our recent study, ARHGEF10, known as a guanine nucleotide exchange factor (GEF) for RhoA, was indicated to interact with Rab6A and Rab8A, which are known to function in the exocytotic pathway, and colocalized with these Rabs at exocytotic vesicles. Moreover, it was suggested that ARHGEF10 is involved in the regulation of Rab6A and Rab8A localization and invasion of breast carcinoma cells, in which Rab8 also acts via regulation of membrane trafficking. These results may reveal the existence of a novel small GTPase cascade which connects the signaling of these Rabs with RhoA during membrane trafficking. In this mini-review, we consider the possible functions of ARHGEF10 and RhoA in the Rab6- and Rab8-mediated membrane trafficking pathway.
小GTP酶在维持细胞内稳态环境和细胞的适当运动中发挥着关键作用。在这些过程中，不同的小GTP酶之间可能需要直接或间接相互作用来调节相互的信号通路。在我们最近的研究中，已知作为RhoA的鸟嘌呤核苷酸交换因子（GEF）的ARHGEF10被表明与Rab6A和Rab8A相互作用，Rab6A和Rab8A已知在胞吐途径中发挥作用，并与这些Rab在胞吐小泡处共定位。此外，有人提出ARHGEF10参与调节Rab6A和Rab8A的定位以及乳腺癌细胞的侵袭，其中Rab8也通过调节膜运输发挥作用。这些结果可能揭示了一种新型小GTP酶级联的存在，该级联在膜运输过程中将这些Rab的信号与RhoA连接起来。在本综述中，我们探讨了ARHGEF10和RhoA在Rab6和Rab8介导的膜运输途径中的可能功能。
