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Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers

Osh/Orp proteins transport sterols between organelles and are involved in phosphoinositide metabolism. The link between these two aspects remains elusive. Using novel assays, we address the influence of membrane composition on the ability of Osh4p/Kes1p to extract, deliver, or transport dehydroergos...

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Detalles Bibliográficos
Autores principales: de Saint-Jean, Maud, Delfosse, Vanessa, Douguet, Dominique, Chicanne, Gaëtan, Payrastre, Bernard, Bourguet, William, Antonny, Bruno, Drin, Guillaume
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241724/
https://www.ncbi.nlm.nih.gov/pubmed/22162133
http://dx.doi.org/10.1083/jcb.201104062
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author de Saint-Jean, Maud
Delfosse, Vanessa
Douguet, Dominique
Chicanne, Gaëtan
Payrastre, Bernard
Bourguet, William
Antonny, Bruno
Drin, Guillaume
author_facet de Saint-Jean, Maud
Delfosse, Vanessa
Douguet, Dominique
Chicanne, Gaëtan
Payrastre, Bernard
Bourguet, William
Antonny, Bruno
Drin, Guillaume
author_sort de Saint-Jean, Maud
collection PubMed
description Osh/Orp proteins transport sterols between organelles and are involved in phosphoinositide metabolism. The link between these two aspects remains elusive. Using novel assays, we address the influence of membrane composition on the ability of Osh4p/Kes1p to extract, deliver, or transport dehydroergosterol (DHE). Surprisingly, phosphatidylinositol 4-phosphate (PI(4)P) specifically inhibited DHE extraction because PI(4)P was itself efficiently extracted by Osh4p. We solve the structure of the Osh4p–PI(4)P complex and reveal how Osh4p selectively substitutes PI(4)P for sterol. Last, we show that Osh4p quickly exchanges DHE for PI(4)P and, thereby, can transport these two lipids between membranes along opposite routes. These results suggest a model in which Osh4p transports sterol from the ER to late compartments pinpointed by PI(4)P and, in turn, transports PI(4)P backward. Coupled to PI(4)P metabolism, this transport cycle would create sterol gradients. Because the residues that recognize PI(4)P are conserved in Osh4p homologues, other Osh/Orp are potential sterol/phosphoinositol phosphate exchangers.
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spelling pubmed-32417242012-06-12 Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers de Saint-Jean, Maud Delfosse, Vanessa Douguet, Dominique Chicanne, Gaëtan Payrastre, Bernard Bourguet, William Antonny, Bruno Drin, Guillaume J Cell Biol Research Articles Osh/Orp proteins transport sterols between organelles and are involved in phosphoinositide metabolism. The link between these two aspects remains elusive. Using novel assays, we address the influence of membrane composition on the ability of Osh4p/Kes1p to extract, deliver, or transport dehydroergosterol (DHE). Surprisingly, phosphatidylinositol 4-phosphate (PI(4)P) specifically inhibited DHE extraction because PI(4)P was itself efficiently extracted by Osh4p. We solve the structure of the Osh4p–PI(4)P complex and reveal how Osh4p selectively substitutes PI(4)P for sterol. Last, we show that Osh4p quickly exchanges DHE for PI(4)P and, thereby, can transport these two lipids between membranes along opposite routes. These results suggest a model in which Osh4p transports sterol from the ER to late compartments pinpointed by PI(4)P and, in turn, transports PI(4)P backward. Coupled to PI(4)P metabolism, this transport cycle would create sterol gradients. Because the residues that recognize PI(4)P are conserved in Osh4p homologues, other Osh/Orp are potential sterol/phosphoinositol phosphate exchangers. The Rockefeller University Press 2011-12-12 /pmc/articles/PMC3241724/ /pubmed/22162133 http://dx.doi.org/10.1083/jcb.201104062 Text en © 2011 de Saint-Jean 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
de Saint-Jean, Maud
Delfosse, Vanessa
Douguet, Dominique
Chicanne, Gaëtan
Payrastre, Bernard
Bourguet, William
Antonny, Bruno
Drin, Guillaume
Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers
title Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers
title_full Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers
title_fullStr Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers
title_full_unstemmed Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers
title_short Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers
title_sort osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241724/
https://www.ncbi.nlm.nih.gov/pubmed/22162133
http://dx.doi.org/10.1083/jcb.201104062
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