Glycobiology World Congress

Biography

Biography: Claudia Koch-Brandt

Abstract

Clusterin (CLU), also known as ApolipoproteinJ (ApoJ) is a highly glycosylated extracellular chaperone. In humans it is expressed in a broad spectrum of tissues and related to a plethora of pathophysiological processes, such as M. Alzheimer, atherosclerosis and cancer, where the protein exerts a cytoprotective role. In its dominant form it is expressed as a secretory protein (sCLU) which during maturation is N-glycosylated and cleaved intracellularly into an α- and a β-chain connected by five symmetrical disulfide bonds. In early studies we examined the role of the carbohydrate moieties in the vectorial secretion of ApoJ at the apical surface of polarized epithelial cells. If N-glycosylation is inhibited by tunicamycin treatment the protein is secreted in equal amounts at both cell surfaces, demonstrating that the carbohydrates are dispensible for the acquisition of a transport competent conformation, however indicating a role of the carbohydrate moieties in the vectorial transport of this protein. Recently, it has been demonstrated that besides the predominant sCLU, rare intracellular CLU forms are expressed in stressed cells. Since these isoforms do not enter nor complete the secretory pathway, they display either no or only core glycosylation and are not proteolytically processed. Due to their sparsity, these intracellular forms are functionally poorly characterized. To evaluate the function(s) of these stress-induced intracellular forms, we first examined whether these isoforms display chaperone activity, to then investigate the impact of glycosylation and proteolytic maturation on this activity.