Intracellular Localization and Mechanisms of Regulation of Phosphatidylinositol Transfer Protein in Swiss Mouse 3T3 Cells

Abstract

Proteins which are able to catalyze the transfer of phospholipid molecules between membranes have been purified and characterized from a wide spectrum of cells and tissues [reviewed by K.W.A. Wirtz, 1991]. Phospholipid transfer proteins with different specificities toward polar headgroups of phospholipids include the phosphatidylcholine transfer protein (PC-TP) which specifically binds and transfers PC [Kamp et al. 1973; Lumb et al., 1976] and the phosphatidylinositol transfer protein (PI-TP) which binds and transfers PI, and to a lesser extent PC [Helmkamp et al.,1974; Demel et al.,1977; DiCorletto et al., 1974]. In addition, a non-specific lipid transfer protein (identical to sterol carrier protein 2) has been identified which catalyzes the transfer of phospholipids and cholesterol between membranes [Bloj and Zilversmit, 1977; Crain and Zilversmit, 1980]. The characteristics of these proteins have been studied in vitro. However, the physiological function of the phospholipid transfer proteins is not yet clear. In mammalian cells most phospholipids are synthesized on the endoplasmic reticulum. This implies that specific mechanisms of transport must operate to redistribute phospholipids from the site of synthesis to the proper localization in the cell. It has been suggested that the phospholipid transfer proteins are involved in these transport processes. Our investigation is focussed on mammalian PI-TP, which is believed to be involved in the intracellular transport processes, particularly pertaining to those membranes that have an active PI metabolism [Wirtz et al., 1987; van Paridon et al., 1987; Cleves et al., 1991] Presumably, transfer of PI to these membranes occurs by PI-TP directly or by flow of membrane vesicles, the PI content of which has been modulated by PI-TP. Recently, the interest in the physiological role of PI-TP has strongly increased with the observation that PI-TP in yeast is identical to the SEC14 protein.