Glycolipid transfer protein: Clear structure and activity, but enigmatic function

Abstract

Glycosphingolipids comprize a small (typically 5–10% by weight) but vital fraction of membrane lipids in eukaryotes (Holthuis et al., 2001). They provide the plasma membrane with chemical and mechanical stabilities and take part in fundamental biological processes including differentiation, cell–cell interaction, and transmembrane signaling. For these lipids, as for most lipids in general, local metabolism and selective transport are important determinants (Sprong et al., 2001). Little is known about these processes, but it is clear that several key players in the organization and control of sphingolipid composition remain to be identified. A protein purified from bovine spleen cytosol specifically transferring glycolipids was already described more than 20 years ago ([Metz and Radin, 1980] and [Radin and Metz, 1982]). An absolute specificity was found for glycolipids containing a β-linked sugar to the hydrophobic backbone (Yamada et al., 1986). Glycolipid transfer proteins (GLTPs, EC number not assigned) are water-soluble proteins of average size of 24 kDa that have been studied extensively in vitro ([Abe and Sasaki, 1985], [Abe et al., 1982], [Brown et al., 1990], [Gammon et al., 1987] and [Metz and Radin, 1982]). Very recently, their structural and in vitro functional properties were reviewed in detail (Brown and Mattjus, 2007). These proteins have been isolated from different sources ranging from spinach chloroplasts to mammalian brain, liver and kidney ([Brown et al., 1990], [Sasaki, 1985] and [Sasaki, 1990]). GLTP orthologs in fungi and plants were found to be involved in programmed cell death ([Brodersen et al., 2002], [Mattjus et al., 2003] and [Saupe et al., 1994]) but their function in mammals is largely unknown. The activity of GLTP is preserved after expression in E. coli ([Godi et al., 2004], Lin et al., 2000 X. Lin, P. Mattjus, H.M. Pike, A.J. Windebank and R.E. Brown, Cloning and expression of glycolipid transfer protein from bovine and porcine brain, J Biol Chem 275 (2000), pp. 5104–5110. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (32)[Lin et al., 2000], [Malinina et al., 2004] and [Rao et al., 2004]) allowing for detailed structure–function studies in vitro.