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Use of mass spectrometry-based lipidomics to probe PITP? (phosphatidylinositol transfer protein ?) function inside the nuclei of PITP?+/+ and PITP?-/- cells

Hunt, A.N., Alb, J.G., Koster, G., Postle, A.D. and Bankaitis, V.A. (2004) Use of mass spectrometry-based lipidomics to probe PITP? (phosphatidylinositol transfer protein ?) function inside the nuclei of PITP?+/+ and PITP?-/- cells Biochemical Society Transactions, 32, (6), pp. 1063-1065. (doi:10.1042/BST0321063).

Record type: Article


The mammalian phospholipid exchange protein PITPa (phosphatidylinositol transfer protein alpha), found in both extranuclear and endonuclear compartments, is thought in part to facilitate nuclear import of the PtdIns (phosphatidylinositol) consumed in the generation of proliferation-associated endonuclear diacylglycerol accumulations. Unlike phosphatidylcholine, endonuclear PtdIns is not synthesized in situ. However, despite progressive postnatal lethality of PITPa ablation in mice, PITPa-/- MEF (mouse embryonic fibroblasts) lack an obviously impaired proliferative capacity. We used ESI-MS (tandem electrospray ionization-MS) to monitor incorporation of the deuterated phospholipid precursors, choline-d9 and inositol-d6, into molecular species of whole cell and endonuclear phosphatidylcholine and PtdIns over 24 h to assess the contribution of PITPa to the nuclear import of PtdIns into MEF cells. In cells labelled for 1, 3, 6, 12 and 24 h fractional inositol-d6 incorporation into whole-cell PtdIns species was consistently higher in PITPa-/- MEF implying greater flux through its biosynthetic pathway. Moreover, endonuclear accumulation of PtdIns-d6 was apparent in the PITPa-/- cells and mirrored that in PITPa+/+ cells. Together, these results suggest that the essential endonuclear PtdIns import via PITPa can be accommodated by other mechanisms.

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Published date: December 2004
Additional Information: Research Colloquia at BioScience2004
Keywords: endonuclear, lipidomics, mouse embryonic fibroblasts, phosphatidylinositol, transfer protein


Local EPrints ID: 27168
ISSN: 0300-5127
PURE UUID: 1018648d-ba3a-423a-999d-aeb5f3a1e0c1
ORCID for A.N. Hunt: ORCID iD
ORCID for A.D. Postle: ORCID iD

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Date deposited: 26 Apr 2006
Last modified: 17 Jul 2017 16:05

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Author: A.N. Hunt ORCID iD
Author: J.G. Alb
Author: G. Koster
Author: A.D. Postle ORCID iD
Author: V.A. Bankaitis

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