A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport
Sterol traffic between the endoplasmic reticulum (ER) and plasma membrane (PM) is a fundamental cellular process that occurs by a poorly understood non-vesicular mechanism. We identified a novel, evolutionarily diverse family of ER membrane proteins with StART-like lipid transfer domains and studied...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/07253 |
| _version_ | 1811236878059307008 |
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| author | Alberto T Gatta Louise H Wong Yves Y Sere Diana M Calderón-Noreña Shamshad Cockcroft Anant K Menon Tim P Levine |
| author_facet | Alberto T Gatta Louise H Wong Yves Y Sere Diana M Calderón-Noreña Shamshad Cockcroft Anant K Menon Tim P Levine |
| author_sort | Alberto T Gatta |
| collection | DOAJ |
| description | Sterol traffic between the endoplasmic reticulum (ER) and plasma membrane (PM) is a fundamental cellular process that occurs by a poorly understood non-vesicular mechanism. We identified a novel, evolutionarily diverse family of ER membrane proteins with StART-like lipid transfer domains and studied them in yeast. StART-like domains from Ysp2p and its paralog Lam4p specifically bind sterols, and Ysp2p, Lam4p and their homologs Ysp1p and Sip3p target punctate ER-PM contact sites distinct from those occupied by known ER-PM tethers. The activity of Ysp2p, reflected in amphotericin-sensitivity assays, requires its second StART-like domain to be positioned so that it can reach across ER-PM contacts. Absence of Ysp2p, Ysp1p or Sip3p reduces the rate at which exogenously supplied sterols traffic from the PM to the ER. Our data suggest that these StART-like proteins act in trans to mediate a step in sterol exchange between the PM and ER. |
| first_indexed | 2024-04-12T12:16:42Z |
| format | Article |
| id | doaj.art-5e7eaabd41d4422a863124ee74eb6141 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:16:42Z |
| publishDate | 2015-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5e7eaabd41d4422a863124ee74eb61412022-12-22T03:33:25ZengeLife Sciences Publications LtdeLife2050-084X2015-05-01410.7554/eLife.07253A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transportAlberto T Gatta0https://orcid.org/0000-0002-2404-7351Louise H Wong1Yves Y Sere2Diana M Calderón-Noreña3Shamshad Cockcroft4Anant K Menon5https://orcid.org/0000-0001-6924-2698Tim P Levine6Department of Cell Biology, UCL Institute of Ophthalmology, London, United KingdomDepartment of Cell Biology, UCL Institute of Ophthalmology, London, United KingdomDepartment of Biochemistry, Weill Cornell Medical College, New York, United StatesDepartment of Biochemistry, Weill Cornell Medical College, New York, United StatesDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United KingdomDepartment of Biochemistry, Weill Cornell Medical College, New York, United StatesDepartment of Cell Biology, UCL Institute of Ophthalmology, London, United KingdomSterol traffic between the endoplasmic reticulum (ER) and plasma membrane (PM) is a fundamental cellular process that occurs by a poorly understood non-vesicular mechanism. We identified a novel, evolutionarily diverse family of ER membrane proteins with StART-like lipid transfer domains and studied them in yeast. StART-like domains from Ysp2p and its paralog Lam4p specifically bind sterols, and Ysp2p, Lam4p and their homologs Ysp1p and Sip3p target punctate ER-PM contact sites distinct from those occupied by known ER-PM tethers. The activity of Ysp2p, reflected in amphotericin-sensitivity assays, requires its second StART-like domain to be positioned so that it can reach across ER-PM contacts. Absence of Ysp2p, Ysp1p or Sip3p reduces the rate at which exogenously supplied sterols traffic from the PM to the ER. Our data suggest that these StART-like proteins act in trans to mediate a step in sterol exchange between the PM and ER.https://elifesciences.org/articles/07253membrane contact sitelipid trafficcholesterolergosterolStART proteinpolyene |
| spellingShingle | Alberto T Gatta Louise H Wong Yves Y Sere Diana M Calderón-Noreña Shamshad Cockcroft Anant K Menon Tim P Levine A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport eLife membrane contact site lipid traffic cholesterol ergosterol StART protein polyene |
| title | A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport |
| title_full | A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport |
| title_fullStr | A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport |
| title_full_unstemmed | A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport |
| title_short | A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport |
| title_sort | new family of start domain proteins at membrane contact sites has a role in er pm sterol transport |
| topic | membrane contact site lipid traffic cholesterol ergosterol StART protein polyene |
| url | https://elifesciences.org/articles/07253 |
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