Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway

Abstract Nε-lysine acetylation in the ER is an essential component of the quality control machinery. ER acetylation is ensured by a membrane transporter, AT-1/SLC33A1, which translocates cytosolic acetyl-CoA into the ER lumen, and two acetyltransferases, ATase1 and ATase2, which acetylate nascent po...

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Autores principales:	Inca A. Dieterich, Yusi Cui, Megan M. Braun, Alexis J. Lawton, Nicklaus H. Robinson, Jennifer L. Peotter, Qing Yu, Jason C. Casler, Benjamin S. Glick, Anjon Audhya, John M. Denu, Lingjun Li, Luigi Puglielli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/467b0be5ab394a82a7cfe0300b131b61
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spelling	oai:doaj.org-article:467b0be5ab394a82a7cfe0300b131b612021-12-02T13:50:41ZAcetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway10.1038/s41598-021-81447-62045-2322https://doaj.org/article/467b0be5ab394a82a7cfe0300b131b612021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81447-6https://doaj.org/toc/2045-2322Abstract Nε-lysine acetylation in the ER is an essential component of the quality control machinery. ER acetylation is ensured by a membrane transporter, AT-1/SLC33A1, which translocates cytosolic acetyl-CoA into the ER lumen, and two acetyltransferases, ATase1 and ATase2, which acetylate nascent polypeptides within the ER lumen. Dysfunctional AT-1, as caused by gene mutation or duplication events, results in severe disease phenotypes. Here, we used two models of AT-1 dysregulation to investigate dynamics of the secretory pathway: AT-1 sTg, a model of systemic AT-1 overexpression, and AT-1S113R/+, a model of AT-1 haploinsufficiency. The animals displayed reorganization of the ER, ERGIC, and Golgi apparatus. In particular, AT-1 sTg animals displayed a marked delay in Golgi-to-plasma membrane protein trafficking, significant alterations in Golgi-based N-glycan modification, and a marked expansion of the lysosomal network. Collectively our results indicate that AT-1 is essential to maintain proper organization and engagement of the secretory pathway.Inca A. DieterichYusi CuiMegan M. BraunAlexis J. LawtonNicklaus H. RobinsonJennifer L. PeotterQing YuJason C. CaslerBenjamin S. GlickAnjon AudhyaJohn M. DenuLingjun LiLuigi PuglielliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Inca A. Dieterich Yusi Cui Megan M. Braun Alexis J. Lawton Nicklaus H. Robinson Jennifer L. Peotter Qing Yu Jason C. Casler Benjamin S. Glick Anjon Audhya John M. Denu Lingjun Li Luigi Puglielli Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway
description	Abstract Nε-lysine acetylation in the ER is an essential component of the quality control machinery. ER acetylation is ensured by a membrane transporter, AT-1/SLC33A1, which translocates cytosolic acetyl-CoA into the ER lumen, and two acetyltransferases, ATase1 and ATase2, which acetylate nascent polypeptides within the ER lumen. Dysfunctional AT-1, as caused by gene mutation or duplication events, results in severe disease phenotypes. Here, we used two models of AT-1 dysregulation to investigate dynamics of the secretory pathway: AT-1 sTg, a model of systemic AT-1 overexpression, and AT-1S113R/+, a model of AT-1 haploinsufficiency. The animals displayed reorganization of the ER, ERGIC, and Golgi apparatus. In particular, AT-1 sTg animals displayed a marked delay in Golgi-to-plasma membrane protein trafficking, significant alterations in Golgi-based N-glycan modification, and a marked expansion of the lysosomal network. Collectively our results indicate that AT-1 is essential to maintain proper organization and engagement of the secretory pathway.
format	article
author	Inca A. Dieterich Yusi Cui Megan M. Braun Alexis J. Lawton Nicklaus H. Robinson Jennifer L. Peotter Qing Yu Jason C. Casler Benjamin S. Glick Anjon Audhya John M. Denu Lingjun Li Luigi Puglielli
author_facet	Inca A. Dieterich Yusi Cui Megan M. Braun Alexis J. Lawton Nicklaus H. Robinson Jennifer L. Peotter Qing Yu Jason C. Casler Benjamin S. Glick Anjon Audhya John M. Denu Lingjun Li Luigi Puglielli
author_sort	Inca A. Dieterich
title	Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway
title_short	Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway
title_full	Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway
title_fullStr	Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway
title_full_unstemmed	Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway
title_sort	acetyl-coa flux from the cytosol to the er regulates engagement and quality of the secretory pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/467b0be5ab394a82a7cfe0300b131b61
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Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway

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