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Cells 2018, 7(11), 211; https://doi.org/10.3390/cells7110211

The Intermolecular Interaction of Ephexin4 Leads to Autoinhibition by Impeding Binding of RhoG

1
School of Life Sciences and Aging Research Institute, Gwangju Institute of Science and Technology, Gwangju 61005, Korea
2
Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, Korea
3
Department of Oncology, College of Medicine, Korea University, Seoul 08308, Korea
*
Author to whom correspondence should be addressed.
Received: 27 September 2018 / Revised: 2 November 2018 / Accepted: 9 November 2018 / Published: 15 November 2018
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Abstract

Ephexin4 is a guanine nucleotide-exchange factor (GEF) for RhoG and is involved in various RhoG-related cellular processes such as phagocytosis of apoptotic cells and migration of cancer cells. Ephexin4 forms an oligomer via an intermolecular interaction, and its GEF activity is increased in the presence of Elmo, an Ephexin4-interacting protein. However, it is uncertain if and how Ephexin4 is autoinhibited. Here, using an Ephexin4 mutant that abrogated the intermolecular interaction, we report that this interaction impeded binding of RhoG to Ephexin4 and thus inhibited RhoG activation. Mutation of the glutamate residue at position 295, which is a highly conserved residue located in the region of Ephexin4 required for the intermolecular interaction, to alanine (Ephexin4E295A) disrupted the intermolecular interaction and increased binding of RhoG, resulting in augmented RhoG activation. In addition, phagocytosis of apoptotic cells and formation of membrane ruffles were increased more by expression of Ephexin4E295A than by expression of wild-type Ephexin4. Taken together, our data suggest that Ephexin4 is autoinhibited through its intermolecular interaction, which impedes binding of RhoG. View Full-Text
Keywords: Ephexin4; Ephexin; GEF; RhoG; autoinhibition; interaction Ephexin4; Ephexin; GEF; RhoG; autoinhibition; interaction
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Kim, K.; Lee, J.; Moon, H.; Lee, S.-A.; Kim, D.; Yang, S.; Lee, D.-H.; Lee, G.; Park, D. The Intermolecular Interaction of Ephexin4 Leads to Autoinhibition by Impeding Binding of RhoG. Cells 2018, 7, 211.

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