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Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus

Sac1 is a phosphoinositide phosphatase of the endoplasmic reticulum and Golgi apparatus that controls organelle membrane composition principally via regulation of phosphatidylinositol 4-phosphate signaling. We present a characterization of the structure of the N-terminal portion of yeast Sac1, conta...

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Autores principales: Cai, Yiying, Deng, Yongqiang, Horenkamp, Florian, Reinisch, Karin M., Burd, Christopher G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137058/
https://www.ncbi.nlm.nih.gov/pubmed/25113029
http://dx.doi.org/10.1083/jcb.201404041
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author Cai, Yiying
Deng, Yongqiang
Horenkamp, Florian
Reinisch, Karin M.
Burd, Christopher G.
author_facet Cai, Yiying
Deng, Yongqiang
Horenkamp, Florian
Reinisch, Karin M.
Burd, Christopher G.
author_sort Cai, Yiying
collection PubMed
description Sac1 is a phosphoinositide phosphatase of the endoplasmic reticulum and Golgi apparatus that controls organelle membrane composition principally via regulation of phosphatidylinositol 4-phosphate signaling. We present a characterization of the structure of the N-terminal portion of yeast Sac1, containing the conserved Sac1 homology domain, in complex with Vps74, a phosphatidylinositol 4-kinase effector and the orthologue of human GOLPH3. The interface involves the N-terminal subdomain of the Sac1 homology domain, within which mutations in the related Sac3/Fig4 phosphatase have been linked to Charcot–Marie–Tooth disorder CMT4J and amyotrophic lateral sclerosis. Disruption of the Sac1–Vps74 interface results in a broader distribution of phosphatidylinositol 4-phosphate within the Golgi apparatus and failure to maintain residence of a medial Golgi mannosyltransferase. The analysis prompts a revision of the membrane-docking mechanism for GOLPH3 family proteins and reveals how an effector of phosphoinositide signaling serves a dual function in signal termination.
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spelling pubmed-41370582015-02-18 Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus Cai, Yiying Deng, Yongqiang Horenkamp, Florian Reinisch, Karin M. Burd, Christopher G. J Cell Biol Research Articles Sac1 is a phosphoinositide phosphatase of the endoplasmic reticulum and Golgi apparatus that controls organelle membrane composition principally via regulation of phosphatidylinositol 4-phosphate signaling. We present a characterization of the structure of the N-terminal portion of yeast Sac1, containing the conserved Sac1 homology domain, in complex with Vps74, a phosphatidylinositol 4-kinase effector and the orthologue of human GOLPH3. The interface involves the N-terminal subdomain of the Sac1 homology domain, within which mutations in the related Sac3/Fig4 phosphatase have been linked to Charcot–Marie–Tooth disorder CMT4J and amyotrophic lateral sclerosis. Disruption of the Sac1–Vps74 interface results in a broader distribution of phosphatidylinositol 4-phosphate within the Golgi apparatus and failure to maintain residence of a medial Golgi mannosyltransferase. The analysis prompts a revision of the membrane-docking mechanism for GOLPH3 family proteins and reveals how an effector of phosphoinositide signaling serves a dual function in signal termination. The Rockefeller University Press 2014-08-18 /pmc/articles/PMC4137058/ /pubmed/25113029 http://dx.doi.org/10.1083/jcb.201404041 Text en © 2014 Cai et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Cai, Yiying
Deng, Yongqiang
Horenkamp, Florian
Reinisch, Karin M.
Burd, Christopher G.
Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus
title Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus
title_full Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus
title_fullStr Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus
title_full_unstemmed Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus
title_short Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus
title_sort sac1–vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the golgi apparatus
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137058/
https://www.ncbi.nlm.nih.gov/pubmed/25113029
http://dx.doi.org/10.1083/jcb.201404041
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