The Golgi-associated retrograde protein (GARP) complex plays an essential role in the maintenance of the Golgi glycosylation machinery

Abstract

The Golgi apparatus is a central hub for intracellular protein trafficking and glycosylation. Steady-state localization of glycosylation enzymes is achieved by a combination of mechanisms involving retention and vesicle recycling, but the machinery governing these mechanisms is poorly understood. Herein we show that the Golgi-associated retrograde protein (GARP) complex is a critical component of this machinery. Using multiple human cell lines, we show that depletion of GARP subunits is detrimental to N- and O-glycosylation, and reduces the stability of glycoproteins and Golgi enzymes. Moreover, GARP-KO cells exhibit impaired retention of glycosylation enzymes in the Golgi. Indeed, a RUSH assay shows that, in GARP-KO cells, the enzyme beta-1,4-galactosyltransferase 1 is not retained at the Golgi but instead is missorted to the endolysosomal compartment. We propose that the endosomal compartment is part of the trafficking itinerary of Golgi enzymes and that the GARP complex is essential for recycling and stabilization of the Golgi glycosylation machinery.