title: Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) binds and transfers phosphatidic acid.
abstract: Phosphatidylinositol transfer proteins (PITPs) are versatile proteins required for signal transduction and membrane traffic. The best characterized mammalian PITPs are the Class I PITPs, PITPα (PITPNA) and PITPβ (PITPNB), which are single domain proteins with a hydrophobic cavity that binds a phosphatidylinositol (PI) or phosphatidylcholine molecule. In this study, we report the lipid binding properties of an uncharacterized soluble PITP, phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) (alternative name, RdgBβ), of the Class II family. We show that the lipid binding properties of this protein are distinct to Class I PITPs because, besides PI, RdgBβ binds and transfers phosphatidic acid (PA) but hardly binds phosphatidylcholine. RdgBβ when purified from Escherichia coli is preloaded with PA and phosphatidylglycerol. When RdgBβ was incubated with permeabilized HL60 cells, phosphatidylglycerol was released, and PA and PI were now incorporated into RdgBβ. After an increase in PA levels following activation of endogenous phospholipase D or after addition of bacterial phospholipase D, binding of PA to RdgBβ was greater at the expense of PI binding. We propose that RdgBβ, when containing PA, regulates an effector protein or can facilitate lipid transfer between membrane compartments.
authors: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6JJ, United Kingdom.
authors: Kathryn
authors: K
authors: Garner
authors: Alan N
authors: AN
authors: Hunt
authors: Grielof
authors: G
authors: Koster
authors: Pentti
authors: P
authors: Somerharju
authors: Emily
authors: E
authors: Groves
authors: Michelle
authors: M
authors: Li
authors: Padinjat
authors: P
authors: Raghu
authors: Roman
authors: R
authors: Holic
authors: Shamshad
authors: S
authors: Cockcroft
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D026901:Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D010712:Phosphatidic Acids / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry; D010739:Phospholipase D / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D008055:Lipids; D026901:Membrane Transport Proteins; C107847:PITPNC1 protein, human; D010712:Phosphatidic Acids; D010715:Phosphatidylglycerols; D010743:Phospholipids; D011994:Recombinant Proteins; D010739:Phospholipase D