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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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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. |
format | Online Article Text |
id | pubmed-4137058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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