Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1

Abstract Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. He...

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Autores principales:	Kwanhyeong Kim, Juyeon Lee, Sang-Ah Lee, Hyunji Moon, Boyeon Park, Deokhwan Kim, Young-Eun Joo, Daeho Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b45c903de0bc48c98bb1fcbc24f70091
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spelling	oai:doaj.org-article:b45c903de0bc48c98bb1fcbc24f700912021-12-02T12:32:26ZIntermolecular steric inhibition of Ephexin4 is relieved by Elmo110.1038/s41598-017-04810-62045-2322https://doaj.org/article/b45c903de0bc48c98bb1fcbc24f700912017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04810-6https://doaj.org/toc/2045-2322Abstract Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. Here, we report a mechanism by which Elmo1 cooperates with Ephexin4 to activate RhoG. We found that Ephexin4 activity was increased by elimination of its SH3 domain which intermolecularly interacts with the N20 region of Ephexin4. This interaction prevented RhoG from binding to Ephexin4 and thus inhibited RhoG activation. Moreover, we also found that Elmo1 associated with the SH3 domain as well as the N20 region and competed with the SH3 domain for binding to the N20 region, interrupting the interaction of the SH3 domain with the N20 region and thereby promoting RhoG binding to Ephexin4. In addition, the activity of Ephexin4 lacking the SH3 domain was comparable to that of Ephexin4 with Elmo1. Taken together, the data suggest that Elmo1 relieves the steric hindrance of Ephexin4 generated by the intermolecular interaction of the SH3 domain and makes Ephexin4 more accessible to RhoG.Kwanhyeong KimJuyeon LeeSang-Ah LeeHyunji MoonBoyeon ParkDeokhwan KimYoung-Eun JooDaeho ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kwanhyeong Kim Juyeon Lee Sang-Ah Lee Hyunji Moon Boyeon Park Deokhwan Kim Young-Eun Joo Daeho Park Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1
description	Abstract Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. Here, we report a mechanism by which Elmo1 cooperates with Ephexin4 to activate RhoG. We found that Ephexin4 activity was increased by elimination of its SH3 domain which intermolecularly interacts with the N20 region of Ephexin4. This interaction prevented RhoG from binding to Ephexin4 and thus inhibited RhoG activation. Moreover, we also found that Elmo1 associated with the SH3 domain as well as the N20 region and competed with the SH3 domain for binding to the N20 region, interrupting the interaction of the SH3 domain with the N20 region and thereby promoting RhoG binding to Ephexin4. In addition, the activity of Ephexin4 lacking the SH3 domain was comparable to that of Ephexin4 with Elmo1. Taken together, the data suggest that Elmo1 relieves the steric hindrance of Ephexin4 generated by the intermolecular interaction of the SH3 domain and makes Ephexin4 more accessible to RhoG.
format	article
author	Kwanhyeong Kim Juyeon Lee Sang-Ah Lee Hyunji Moon Boyeon Park Deokhwan Kim Young-Eun Joo Daeho Park
author_facet	Kwanhyeong Kim Juyeon Lee Sang-Ah Lee Hyunji Moon Boyeon Park Deokhwan Kim Young-Eun Joo Daeho Park
author_sort	Kwanhyeong Kim
title	Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1
title_short	Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1
title_full	Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1
title_fullStr	Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1
title_full_unstemmed	Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1
title_sort	intermolecular steric inhibition of ephexin4 is relieved by elmo1
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b45c903de0bc48c98bb1fcbc24f70091
work_keys_str_mv	AT kwanhyeongkim intermolecularstericinhibitionofephexin4isrelievedbyelmo1 AT juyeonlee intermolecularstericinhibitionofephexin4isrelievedbyelmo1 AT sangahlee intermolecularstericinhibitionofephexin4isrelievedbyelmo1 AT hyunjimoon intermolecularstericinhibitionofephexin4isrelievedbyelmo1 AT boyeonpark intermolecularstericinhibitionofephexin4isrelievedbyelmo1 AT deokhwankim intermolecularstericinhibitionofephexin4isrelievedbyelmo1 AT youngeunjoo intermolecularstericinhibitionofephexin4isrelievedbyelmo1 AT daehopark intermolecularstericinhibitionofephexin4isrelievedbyelmo1
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Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1

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