Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily
Sec14, the major yeast phosphatidylinositol (PtdIns)/phosphatidylcholine (PtdCho) transfer protein, regulates essential interfaces between lipid metabolism and membrane trafficking from the trans-Golgi network (TGN). How Sec14 does so remains unclear. We report that Sec14 binds PtdIns and PtdCho at ...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
2008
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| Online Access: | http://hdl.handle.net/20.500.11937/45619 |
| _version_ | 1848757336347246592 |
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| author | Schaaf, G. Ortlund, E. Tyeryar, K. Mousley, Carl Ile, K. Garrett, T. Ren, J. Woolls, M. Raetz, C. Redinbo, M. Bankaitis, V. |
| author_facet | Schaaf, G. Ortlund, E. Tyeryar, K. Mousley, Carl Ile, K. Garrett, T. Ren, J. Woolls, M. Raetz, C. Redinbo, M. Bankaitis, V. |
| author_sort | Schaaf, G. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Sec14, the major yeast phosphatidylinositol (PtdIns)/phosphatidylcholine (PtdCho) transfer protein, regulates essential interfaces between lipid metabolism and membrane trafficking from the trans-Golgi network (TGN). How Sec14 does so remains unclear. We report that Sec14 binds PtdIns and PtdCho at distinct (but overlapping) sites, and both PtdIns- and PtdCho-binding activities are essential Sec14 activities. We further show both activities must reside within the same molecule to reconstitute a functional Sec14 and for effective Sec14-mediated regulation of phosphoinositide homeostasis in vivo. This regulation is uncoupled from PtdIns-transfer activity and argues for an interfacial presentation mode for Sec14-mediated potentiation of PtdIns kinases. Such a regulatory role for Sec14 is a primary counter to action of the Kes1 sterol-binding protein that antagonizes PtdIns 4-OH kinase activity in vivo. Collectively, these findings outline functional mechanisms for the Sec14 superfamily and reveal additional layers of complexity for regulating phosphoinositide homeostasis in eukaryotes. © 2008 Elsevier Inc. All rights reserved. |
| first_indexed | 2025-11-14T09:26:28Z |
| format | Journal Article |
| id | curtin-20.500.11937-45619 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:26:28Z |
| publishDate | 2008 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-456192017-09-13T14:24:48Z Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily Schaaf, G. Ortlund, E. Tyeryar, K. Mousley, Carl Ile, K. Garrett, T. Ren, J. Woolls, M. Raetz, C. Redinbo, M. Bankaitis, V. Sec14, the major yeast phosphatidylinositol (PtdIns)/phosphatidylcholine (PtdCho) transfer protein, regulates essential interfaces between lipid metabolism and membrane trafficking from the trans-Golgi network (TGN). How Sec14 does so remains unclear. We report that Sec14 binds PtdIns and PtdCho at distinct (but overlapping) sites, and both PtdIns- and PtdCho-binding activities are essential Sec14 activities. We further show both activities must reside within the same molecule to reconstitute a functional Sec14 and for effective Sec14-mediated regulation of phosphoinositide homeostasis in vivo. This regulation is uncoupled from PtdIns-transfer activity and argues for an interfacial presentation mode for Sec14-mediated potentiation of PtdIns kinases. Such a regulatory role for Sec14 is a primary counter to action of the Kes1 sterol-binding protein that antagonizes PtdIns 4-OH kinase activity in vivo. Collectively, these findings outline functional mechanisms for the Sec14 superfamily and reveal additional layers of complexity for regulating phosphoinositide homeostasis in eukaryotes. © 2008 Elsevier Inc. All rights reserved. 2008 Journal Article http://hdl.handle.net/20.500.11937/45619 10.1016/j.molcel.2007.11.026 unknown |
| spellingShingle | Schaaf, G. Ortlund, E. Tyeryar, K. Mousley, Carl Ile, K. Garrett, T. Ren, J. Woolls, M. Raetz, C. Redinbo, M. Bankaitis, V. Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily |
| title | Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily |
| title_full | Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily |
| title_fullStr | Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily |
| title_full_unstemmed | Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily |
| title_short | Functional Anatomy of Phospholipid Binding and Regulation of Phosphoinositide Homeostasis by Proteins of the Sec14 Superfamily |
| title_sort | functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the sec14 superfamily |
| url | http://hdl.handle.net/20.500.11937/45619 |