Tissue Specific Transplantation Antigen P35B (= GDP-4-keto-6-D-Deoxymannose Epimerase-Reductase) (TSTA3)

Abstract

The 6-deoxyhexose l-fucose has a wide distribution in nature as component of bacterial, plant, and animal oligo- and polysaccharides. l-fucose is inserted in glycoconjugates by the action of several fucosyltransferases which use GDP-l-fucose as a substrate. The pioneering studies of Ginsburg indicated that GDP-l-fucose is formed by a de novo pathway starting from GDP-d-mannose (Ginsburg 1960, 1961). With few exceptions, this pathway represents the most important source of l-fucose in all kingdoms and the enzymes involved in it are highly conserved. A salvage pathway for GDP-l-fucose is also used to recycle the free sugar derived from exogenous sources or from glycoconjugate turnover (Park et al. 1998; Pastuszak et al. 1998). However, the contribution of the salvage pathway for the supply of intracellular GDP-l-fucose pool is quantitatively less important (Yurchenco and Atkinson 1975). Once formed in the cytosol, GDP-l-fucose is then transferred into the Golgi compartment by means of a specific transporter (Puglielli and Hirschberg 1999). Recent evidences have also suggested that GDP-l-fucose can also enter the ER, but using a different transport system (Ishikawa et al. 2010). Thus, the levels of GDP-l-fucose for the ER/Golgi fucosyltransferases result from both the activity of the two biosynthetic pathways and from the transporter efficiency. Indeed, availability of GDP-l-fucose substrate to the fucosyltransferases represents a mean to modulate fucosylated glycan production (Noda et al. 2003; Niittymäki et al. 2006; Moriwaki et al. 2007).