Ceramides are essential precursors of complex sphingolipids and act as potent signaling molecules. Ceramides are synthesized in the endoplasmic reticulum (ER) and receive their head-groups in the Golgi apparatus, yielding complex sphingolipids (SPs). Transport of ceramides between the ER and the Golgi is executed by the essential ceramide transport protein (CERT) in mammalian cells. However, yeast cells lack a CERT homolog, and the mechanism of ER to Golgi ceramide transport remains largely elusive. Here, we identified a role for yeast Svf1 in ceramide transport between the ER and the Golgi. Svf1 is dynamically targeted to membranes via an N-terminal amphipathic helix (AH). Svf1 binds ceramide via a hydrophobic binding pocket that is located in between two lipocalin domains. We showed that Svf1 membrane-targeting is important to maintain flux of ceramides into complex SPs. Together, our results show that Svf1 is a ceramide binding protein that contributes to sphingolipid metabolism at Golgi compartments.
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March 10 2023
Yeast Svf1 binds ceramides and contributes to sphingolipid metabolism at the ER cis-Golgi interface
Sergej Limar
,
Sergej Limar
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
Department of Biology/Chemistry Bioanalytical Chemistry Section, Osnabrück University
, Osnabrück, Germany
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Carolin Körner
,
Carolin Körner
(Investigation, Methodology)
1
Department of Biology/Chemistry Bioanalytical Chemistry Section, Osnabrück University
, Osnabrück, Germany
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Fernando Martínez-Montañés
,
Fernando Martínez-Montañés
(Investigation)
2
Department of Biochemistry and Molecular Biology Villum Center for Bioanalytical Sciences, University of Southern Denmark
, Odense, Denmark
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Viktoriya G. Stancheva
,
Viktoriya G. Stancheva
(Investigation, Resources, Writing - review & editing)
3
MRC Laboratory of Molecular Biology
, Cambridge, UK
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Verena N. Wolf
,
Verena N. Wolf
(Formal analysis, Investigation)
1
Department of Biology/Chemistry Bioanalytical Chemistry Section, Osnabrück University
, Osnabrück, Germany
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Stefan Walter
,
Stefan Walter
(Methodology)
4
Osnabrück University Center of Cellular Nanoanalytic Osnabrück (CellNanOs)
, Osnabrück, Germany
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Elizabeth A. Miller
,
Elizabeth A. Miller
(Funding acquisition, Investigation, Writing - review & editing)
3
MRC Laboratory of Molecular Biology
, Cambridge, UK
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Christer S. Ejsing
,
Christer S. Ejsing
(Data curation, Formal analysis, Funding acquisition, Investigation, Project administration, Resources, Software, Supervision, Writing - review & editing)
2
Department of Biochemistry and Molecular Biology Villum Center for Bioanalytical Sciences, University of Southern Denmark
, Odense, Denmark
5
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory
, Heidelberg, Germany
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Vanesa Viviana Galassi
,
Vanesa Viviana Galassi
(Investigation)
6
Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo
, Mendoza, Argentina
7
Instituto Interdisciplinario de Ciencias Básicas (ICB), Universidad Nacional de Cuyo, CONICET
, Mendoza, Argentina
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Florian Fröhlich
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
Department of Biology/Chemistry Bioanalytical Chemistry Section, Osnabrück University
, Osnabrück, Germany
4
Osnabrück University Center of Cellular Nanoanalytic Osnabrück (CellNanOs)
, Osnabrück, Germany
Correspondence to Florian Fröhlich: florian.froehlich@uos.de
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Sergej Limar
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Biology/Chemistry Bioanalytical Chemistry Section, Osnabrück University
, Osnabrück, Germany
Carolin Körner
Investigation, Methodology
1
Department of Biology/Chemistry Bioanalytical Chemistry Section, Osnabrück University
, Osnabrück, Germany
Fernando Martínez-Montañés
Investigation
2
Department of Biochemistry and Molecular Biology Villum Center for Bioanalytical Sciences, University of Southern Denmark
, Odense, Denmark
Viktoriya G. Stancheva
Investigation, Resources, Writing - review & editing
3
MRC Laboratory of Molecular Biology
, Cambridge, UK
Verena N. Wolf
Formal analysis, Investigation
1
Department of Biology/Chemistry Bioanalytical Chemistry Section, Osnabrück University
, Osnabrück, Germany
Stefan Walter
Methodology
4
Osnabrück University Center of Cellular Nanoanalytic Osnabrück (CellNanOs)
, Osnabrück, Germany
Elizabeth A. Miller
Funding acquisition, Investigation, Writing - review & editing
3
MRC Laboratory of Molecular Biology
, Cambridge, UK
Christer S. Ejsing
Data curation, Formal analysis, Funding acquisition, Investigation, Project administration, Resources, Software, Supervision, Writing - review & editing
2
Department of Biochemistry and Molecular Biology Villum Center for Bioanalytical Sciences, University of Southern Denmark
, Odense, Denmark
5
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory
, Heidelberg, Germany
Vanesa Viviana Galassi
Investigation
6
Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo
, Mendoza, Argentina
7
Instituto Interdisciplinario de Ciencias Básicas (ICB), Universidad Nacional de Cuyo, CONICET
, Mendoza, Argentina
Florian Fröhlich
Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Biology/Chemistry Bioanalytical Chemistry Section, Osnabrück University
, Osnabrück, Germany
4
Osnabrück University Center of Cellular Nanoanalytic Osnabrück (CellNanOs)
, Osnabrück, Germany
Correspondence to Florian Fröhlich: florian.froehlich@uos.de
Disclosures: The authors declare no competing interests exist.
Received:
September 30 2021
Revision Received:
October 21 2022
Accepted:
February 03 2023
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
Deutsche Forschungsgemeinschaft
- Award Id(s): FR 3647/3-1,FR 3647/4-1,SFB944
Funder(s):
VILLUM Foundation
- Award Id(s): VKR023439
Funder(s):
VILLUM Center for Bioanalytical Sciences
- Award Id(s): VKR023179
Funder(s):
Lundbeckfonden
- Award Id(s): R54-A5858
Funder(s):
UK Medical Research Council
- Award Id(s): MRC_UP_12-1/10
© 2023 Limar et al.
2023
Limar 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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2023) 222 (5): e202109162.
Article history
Received:
September 30 2021
Revision Received:
October 21 2022
Accepted:
February 03 2023
Citation
Sergej Limar, Carolin Körner, Fernando Martínez-Montañés, Viktoriya G. Stancheva, Verena N. Wolf, Stefan Walter, Elizabeth A. Miller, Christer S. Ejsing, Vanesa Viviana Galassi, Florian Fröhlich; Yeast Svf1 binds ceramides and contributes to sphingolipid metabolism at the ER cis-Golgi interface. J Cell Biol 1 May 2023; 222 (5): e202109162. doi: https://doi.org/10.1083/jcb.202109162
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