BBB seminar: Kristian Prydz

Kristian Prydz
Department of Molecular Biosciences, University of Oslo

The dominating view of how the Golgi apparatus is organized favours the opinion that all secretory proteins are exposed to the same set of enzymes and metabolites during transit through the Golgi cisternae. It has remained an enigma why some proteins are uniformly glycosylated in a tissue, while other protein species acquire glycans with a wide variety of structures, even attached to the same amino acid position in the protein cores. We have recently shown that a single protein species can acquire different post-translational glycan modifications in the apical and basolateral secretory pathways of epithelial Madin-Darby canine kidney (MDCK) cells. Even modifications thought to occur early in the secretory pathway differed for the two pathways (Tveit et al. 2005, J Biol Chem 280:29596; Vuong et al. 2006, Glycobiology 16:326 ). These observations indicate a physical separation of the two pathways at an early stage of the secretory pathway. A differential detergent solubility of apical and basolateral proteins in cold Triton X-100 has long been used as a criterion for association with either pathway. Recently, it was reported that a similar partitioning after Tween 20 extraction could be observed for glycoproteins with high-mannose glycan structures, supporting the view that specialized domains had formed already in the endoplasmic reticulum (ER) (Alfalah et al. 2005, J Biol Chem 280:42636). Such physical segregation could be based on adjacent microdomains, or on the dedication of separate stacks of Golgi cisternae to different functions. Recently, the latter possibility gained support from a study in Drosophila , where stacked fragments (units) of the Golgi complex were shown to be functionally diverse (Yano et al. 2005, Proc Natl Acad Sci USA 102:13467). A UDP-sugar transporter, Fringe connection, is shown to be localized to a subset of Golgi units different from that of the sulfotransferase Sulfateless .

Our working hypothesis is that the Golgi apparatus of mammalian cells is segregated into more than one functional unit, with different abilities to modify proteins with glycans. The differences result from differences in the content of enzymes, transporters, and metabolites. The glycoproteome of a particular cell type or tissue is more dependent on the organization of the Golgi apparatus than previously thought.

Host: Jaakko Saraste <jaakko.saraste[@[biomed.uib.no>, Dept. of Biomedicine