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Human atlastin-3 is a constitutive ER membrane fusion catalyst

Homotypic membrane fusion catalyzed by the atlastin (ATL) GTPase sustains the branched endoplasmic reticulum (ER) network in metazoans. Our recent discovery that two of the three human ATL paralogs (ATL1/2) are C-terminally autoinhibited implied that relief of autoinhibition would be integral to the...

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Autores principales: Bryce, Samantha, Stolzer, Maureen, Crosby, Daniel, Yang, Ruijin, Durand, Dannie, Lee, Tina H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140384/
https://www.ncbi.nlm.nih.gov/pubmed/37102997
http://dx.doi.org/10.1083/jcb.202211021
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author Bryce, Samantha
Stolzer, Maureen
Crosby, Daniel
Yang, Ruijin
Durand, Dannie
Lee, Tina H.
author_facet Bryce, Samantha
Stolzer, Maureen
Crosby, Daniel
Yang, Ruijin
Durand, Dannie
Lee, Tina H.
author_sort Bryce, Samantha
collection PubMed
description Homotypic membrane fusion catalyzed by the atlastin (ATL) GTPase sustains the branched endoplasmic reticulum (ER) network in metazoans. Our recent discovery that two of the three human ATL paralogs (ATL1/2) are C-terminally autoinhibited implied that relief of autoinhibition would be integral to the ATL fusion mechanism. An alternative hypothesis is that the third paralog ATL3 promotes constitutive ER fusion with relief of ATL1/2 autoinhibition used conditionally. However, published studies suggest ATL3 is a weak fusogen at best. Contrary to expectations, we demonstrate here that purified human ATL3 catalyzes efficient membrane fusion in vitro and is sufficient to sustain the ER network in triple knockout cells. Strikingly, ATL3 lacks any detectable C-terminal autoinhibition, like the invertebrate Drosophila ATL ortholog. Phylogenetic analysis of ATL C-termini indicates that C-terminal autoinhibition is a recent evolutionary innovation. We suggest that ATL3 is a constitutive ER fusion catalyst and that ATL1/2 autoinhibition likely evolved in vertebrates as a means of upregulating ER fusion activity on demand.
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spelling pubmed-101403842023-10-26 Human atlastin-3 is a constitutive ER membrane fusion catalyst Bryce, Samantha Stolzer, Maureen Crosby, Daniel Yang, Ruijin Durand, Dannie Lee, Tina H. J Cell Biol Article Homotypic membrane fusion catalyzed by the atlastin (ATL) GTPase sustains the branched endoplasmic reticulum (ER) network in metazoans. Our recent discovery that two of the three human ATL paralogs (ATL1/2) are C-terminally autoinhibited implied that relief of autoinhibition would be integral to the ATL fusion mechanism. An alternative hypothesis is that the third paralog ATL3 promotes constitutive ER fusion with relief of ATL1/2 autoinhibition used conditionally. However, published studies suggest ATL3 is a weak fusogen at best. Contrary to expectations, we demonstrate here that purified human ATL3 catalyzes efficient membrane fusion in vitro and is sufficient to sustain the ER network in triple knockout cells. Strikingly, ATL3 lacks any detectable C-terminal autoinhibition, like the invertebrate Drosophila ATL ortholog. Phylogenetic analysis of ATL C-termini indicates that C-terminal autoinhibition is a recent evolutionary innovation. We suggest that ATL3 is a constitutive ER fusion catalyst and that ATL1/2 autoinhibition likely evolved in vertebrates as a means of upregulating ER fusion activity on demand. Rockefeller University Press 2023-04-26 /pmc/articles/PMC10140384/ /pubmed/37102997 http://dx.doi.org/10.1083/jcb.202211021 Text en © 2023 Bryce et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Bryce, Samantha
Stolzer, Maureen
Crosby, Daniel
Yang, Ruijin
Durand, Dannie
Lee, Tina H.
Human atlastin-3 is a constitutive ER membrane fusion catalyst
title Human atlastin-3 is a constitutive ER membrane fusion catalyst
title_full Human atlastin-3 is a constitutive ER membrane fusion catalyst
title_fullStr Human atlastin-3 is a constitutive ER membrane fusion catalyst
title_full_unstemmed Human atlastin-3 is a constitutive ER membrane fusion catalyst
title_short Human atlastin-3 is a constitutive ER membrane fusion catalyst
title_sort human atlastin-3 is a constitutive er membrane fusion catalyst
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140384/
https://www.ncbi.nlm.nih.gov/pubmed/37102997
http://dx.doi.org/10.1083/jcb.202211021
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