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Review
. 2019 May;10(3):169-177.
doi: 10.1080/21541248.2017.1302550. Epub 2017 Apr 27.

Involvement of ARHGEF10, GEF for RhoA, in Rab6/Rab8-mediating membrane traffic

Satoshi Shibata  1 , Yui Teshima  1 , Kenta Niimi  1 , Shinobu Inagaki  1
Affiliations
Review

Involvement of ARHGEF10, GEF for RhoA, in Rab6/Rab8-mediating membrane traffic

Satoshi Shibata et al. Small GTPases. 2019 May.

Abstract

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.

Keywords: ARHGEF10; RabGTPase; RhoGEF; membrane trafficking.

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Figures

Figure 1.
Figure 1.
Schematic representation of ARHGEF10. The region 1–211 amino acids (aa) inhibited ARHGEF10 to localize to the Rab8-positive tubular structure. The region 212–332 aa negatively regulated the GEF activity of ARHGEF10. C-terminous 1304–1342 aa, which does not include the PDZ-binding motif (1343–1345 aa), is an essential region for the GEF activity of ARHGEF10.
Figure 2.
Figure 2.
Schematic representation of exocytotic pathway, which is modulated by Rab6 and Rab8. ARHGEF10 localized to Rab6- and Rab8-positive exocytotic vesicles, but not Rab6-positive Golgi apparatus and Rab8-positive tubular structure. It is possible that RhoA might contribute to the biogenesis of Rab8-positive tubular structure (j RhoA), the fission of exocytotic vesicles from Golgi apparatus (k RhoA), tethering of exocytotic vesicles to plasma membrane (l RhoA), mitotic-spindle formation (m RhoA) and ciliogenesis (m RhoA). Rab6-positive: blue, Rab8-positive: orange, ARHGEF10-positive: brown.
See this image and copyright information in PMC

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