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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2023
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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. |
format | Online Article Text |
id | pubmed-10140384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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