Identification and characterisation of the RalA-ERp57 interaction: evidence for GDI activity of ERp57.

RalA is a membrane-associated small GTPase that regulates vesicle trafficking. Here we identify a specific interaction between RalA and ERp57, an oxidoreductase and signalling protein. ERp57 bound specifically to the GDP-bound form of RalA, but not the GTP-bound form, and inhibited the dissociation...

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Autores principales:	Adam Brymora, Iain G Duggin, Leise A Berven, Ellen M van Dam, Basil D Roufogalis, Phillip J Robinson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e0485c883f5c42108cfec9d7570c0ecf
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spelling	oai:doaj.org-article:e0485c883f5c42108cfec9d7570c0ecf2021-11-18T08:06:39ZIdentification and characterisation of the RalA-ERp57 interaction: evidence for GDI activity of ERp57.1932-620310.1371/journal.pone.0050879https://doaj.org/article/e0485c883f5c42108cfec9d7570c0ecf2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23226417/?tool=EBIhttps://doaj.org/toc/1932-6203RalA is a membrane-associated small GTPase that regulates vesicle trafficking. Here we identify a specific interaction between RalA and ERp57, an oxidoreductase and signalling protein. ERp57 bound specifically to the GDP-bound form of RalA, but not the GTP-bound form, and inhibited the dissociation of GDP from RalA in vitro. These activities were inhibited by reducing agents, but no disulphide bonds were detected between RalA and ERp57. Mutation of all four of ERp57's active site cysteine residues blocked sensitivity to reducing agents, suggesting that redox-dependent conformational changes in ERp57 affect binding to RalA. Mutations in the switch II region of the GTPase domain of RalA specifically reduced or abolished binding to ERp57, but did not block GTP-specific binding to known RalA effectors, the exocyst and RalBP1. Oxidative treatment of A431 cells with H(2)O(2) inhibited cellular RalA activity, and the effect was exacerbated by expression of recombinant ERp57. The oxidative treatment significantly increased the amount of RalA localised to the cytosol. These findings suggest that ERp57 regulates RalA signalling by acting as a redox-sensitive guanine-nucleotide dissociation inhibitor (RalGDI).Adam BrymoraIain G DugginLeise A BervenEllen M van DamBasil D RoufogalisPhillip J RobinsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e50879 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adam Brymora Iain G Duggin Leise A Berven Ellen M van Dam Basil D Roufogalis Phillip J Robinson Identification and characterisation of the RalA-ERp57 interaction: evidence for GDI activity of ERp57.
description	RalA is a membrane-associated small GTPase that regulates vesicle trafficking. Here we identify a specific interaction between RalA and ERp57, an oxidoreductase and signalling protein. ERp57 bound specifically to the GDP-bound form of RalA, but not the GTP-bound form, and inhibited the dissociation of GDP from RalA in vitro. These activities were inhibited by reducing agents, but no disulphide bonds were detected between RalA and ERp57. Mutation of all four of ERp57's active site cysteine residues blocked sensitivity to reducing agents, suggesting that redox-dependent conformational changes in ERp57 affect binding to RalA. Mutations in the switch II region of the GTPase domain of RalA specifically reduced or abolished binding to ERp57, but did not block GTP-specific binding to known RalA effectors, the exocyst and RalBP1. Oxidative treatment of A431 cells with H(2)O(2) inhibited cellular RalA activity, and the effect was exacerbated by expression of recombinant ERp57. The oxidative treatment significantly increased the amount of RalA localised to the cytosol. These findings suggest that ERp57 regulates RalA signalling by acting as a redox-sensitive guanine-nucleotide dissociation inhibitor (RalGDI).
format	article
author	Adam Brymora Iain G Duggin Leise A Berven Ellen M van Dam Basil D Roufogalis Phillip J Robinson
author_facet	Adam Brymora Iain G Duggin Leise A Berven Ellen M van Dam Basil D Roufogalis Phillip J Robinson
author_sort	Adam Brymora
title	Identification and characterisation of the RalA-ERp57 interaction: evidence for GDI activity of ERp57.
title_short	Identification and characterisation of the RalA-ERp57 interaction: evidence for GDI activity of ERp57.
title_full	Identification and characterisation of the RalA-ERp57 interaction: evidence for GDI activity of ERp57.
title_fullStr	Identification and characterisation of the RalA-ERp57 interaction: evidence for GDI activity of ERp57.
title_full_unstemmed	Identification and characterisation of the RalA-ERp57 interaction: evidence for GDI activity of ERp57.
title_sort	identification and characterisation of the rala-erp57 interaction: evidence for gdi activity of erp57.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e0485c883f5c42108cfec9d7570c0ecf
work_keys_str_mv	AT adambrymora identificationandcharacterisationoftheralaerp57interactionevidenceforgdiactivityoferp57 AT iaingduggin identificationandcharacterisationoftheralaerp57interactionevidenceforgdiactivityoferp57 AT leiseaberven identificationandcharacterisationoftheralaerp57interactionevidenceforgdiactivityoferp57 AT ellenmvandam identificationandcharacterisationoftheralaerp57interactionevidenceforgdiactivityoferp57 AT basildroufogalis identificationandcharacterisationoftheralaerp57interactionevidenceforgdiactivityoferp57 AT phillipjrobinson identificationandcharacterisationoftheralaerp57interactionevidenceforgdiactivityoferp57
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Identification and characterisation of the RalA-ERp57 interaction: evidence for GDI activity of ERp57.

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