Use of mass spectrometry-based lipidomics to probe PITPα (phosphatidylinositol transfer protein α) function inside the nuclei of PITPα+/+ and PITPα-/- 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 PITPα (phosphatidylinositol transfer protein α) function inside the nuclei of PITPα+/+ and PITPα-/- cells. Biochemical Society Transactions, 32, (6), 1063-1065. (doi:10.1042/BST0321063).

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Original Publication URL: http://dx.doi.org/10.1042/BST0321063

Description/Abstract

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.

Item Type: Article
Additional Information: Research Colloquia at BioScience2004
ISSNs: 0300-5127 (print)
Related URLs:
Keywords: endonuclear, lipidomics, mouse embryonic fibroblasts, phosphatidylinositol, transfer protein
Subjects: Q Science > QP Physiology
Divisions: University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
ePrint ID: 27168
Date Deposited: 26 Apr 2006
Last Modified: 27 Mar 2014 18:16
Contact Email Address: anh@soton.ac.uk
URI: http://eprints.soton.ac.uk/id/eprint/27168

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