title: Potential role for phosphatidylinositol transfer protein (PITP) family in lipid transfer during phospholipase C signalling.
abstract: The hallmark of mammalian phosphatidylinositol transfer proteins (PITPs) is to transfer phosphatidylinositol between membrane compartments. In the mammalian genome, there are three genes that code for soluble PITP proteins, PITPα, PITPβ and RdgBβ and two genes that code for membrane-associated multi-domain proteins (RdgBαI and II) containing a PITP domain. PITPα and PITPβ constitute Class I PITPs whilst the RdgB proteins constitute Class II proteins based on sequence analysis. The PITP domain of both Class I and II can sequester one molecule of phosphatidylinositol (PI) in its hydrophobic cavity. Therefore, in principle, PITPs are therefore ideally poised to couple phosphatidylinositol delivery to the PI kinases for substrate provision for phospholipases C during cell activation. Since phosphatidylinositol (4,5)bisphosphate plays critical roles in cells, particularly at the plasma membrane, where it is a substrate for both phospholipase C and phosphoinositide-3-kinases as well as required as an intact lipid to regulate ion channels and the actin cytoskeleton, homeostatic mechanisms to maintain phosphatidylinositol(4,5)bisphosphate levels are vital. To maintain phosphatidylinositol levels, phospholipase C activation inevitably leads to the resynthesis of PI at the endoplasmic reticulum where the enzymes are located. Phosphatidic acid generated at the plasma membrane during phospholipase C activation needs to move to the ER for conversion to PI and here we provide evidence that Class II PITPs are also able to bind and transport phosphatidic acid. Thus RdgB proteins could couple PA and PI transport bidirectionally during phospholipase C signalling.
authors.affiliation: Dept. of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, UK. Electronic address: s.cockcroft@ucl.ac.uk.
authors.forename: Shamshad
authors.initials: S
authors.lastname: Cockcroft
authors.forename: Kathryn
authors.initials: K
authors.lastname: Garner
mesh_terms: D000818:Animals; D006801:Humans; D050356:Lipid Metabolism; D005810:Multigene Family; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
chemical_list: D049294:Phospholipid Transfer Proteins; D010738:Type C Phospholipases