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- Title
Phosphoinositide profiling in complex lipid mixtures using electrospray ionization mass spectrometry.
- Authors
Wenk, Markus R; Lucast, Louise; Di Paolo, Gilbert; Romanelli, Anthony J; Suchy, Sharon F; Nussbaum, Robert L; Cline, Gary W; Shulman, Gerald I; McMurray, Walter; De Camilli, Pietro
- Abstract
Phosphoinositides (phosphorylated derivatives of phosphatidylinositol, PI) are versatile intracellular signaling lipids whose occurrence in low concentrations complicates direct mass measurements[SUP1-3]. Here we present a sensitive method to detect, identify and quantify phosphatidylinositol (phosphate (PIP) and phosphatidylinositol bisphosphate (PIP[SUB2]) with different fatty acid compositions (phosphoinositide profiles) in total lipid extracts by electrospray ionization mass spectrometry (ESI-MS). Using this method, we detected (elevated concentrations of PIP[SUB2] in human fibroblasts from patients with Lowe syndrome, a genetic disorder that affects phosphoinositide metabolism[SUP4]. Saccharomyces cerevisiae cells deficient in enzymes involved in PIP metabolism-Sac1p, a phosphoinositide phosphatase[SUP5], and Vps34p and Pik1p, a PI 3-kinase[SUP6] and PI 4-kinase[SUP7], respectively-showed not only different PIP concentrations but also differential changes in PIP profiles indicating metabolic and/or subcellular pooling. Mass spectrometric analysis of phosphoinositides offers unique advantages over existing approaches and may represent a powerful diagnostic tool for human diseases that involve defective phosphoinositide metabolism.
- Subjects
PHOSPHOINOSITIDES; GENETIC disorders; LOWE'S syndrome; MASS spectrometry; LIPIDS
- Publication
Nature Biotechnology, 2003, Vol 21, Issue 7, p813
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt837