Genetic ablation of phosphatidylinositol transfer protein function in murine embryonic stem cells

Molecular Biology of the Cell
James G AlbV A Bankaitis

Abstract

Phosphatidylinositol transfer proteins (PITPs) regulate the interface between signal transduction, membrane-trafficking, and lipid metabolic pathways in eukaryotic cells. The best characterized mammalian PITPs are PITP alpha and PITP beta, two highly homologous proteins that are encoded by distinct genes. Insights into PITP alpha and PITP beta function in mammalian systems have been gleaned exclusively from cell-free or permeabilized cell reconstitution and resolution studies. Herein, we report for the first time the use of genetic approaches to directly address the physiological functions of PITP alpha and PITP beta in murine cells. Contrary to expectations, we find that ablation of PITP alpha function in murine cells fails to compromise growth and has no significant consequence for bulk phospholipid metabolism. Moreover, the data show that PITP alpha does not play an obvious role in any of the cellular activities where it has been reconstituted as an essential stimulatory factor. These activities include protein trafficking through the constitutive secretory pathway, endocytic pathway function, biogenesis of mast cell dense core secretory granules, and the agonist-induced fusion of dense core secretory granules to the mast ce...Continue Reading

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Citations

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Apr 6, 2004·Biochemical and Biophysical Research Communications·Marie E MonacoPaul D Walden
Jul 24, 2012·The Journal of Biological Chemistry·Kathryn GarnerShamshad Cockcroft
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Jul 11, 2006·FEBS Letters·Karel W A Wirtz
Oct 29, 2002·FEBS Letters·Victoria Allen-BaumeShamshad Cockcroft
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