A role of GCC88 in the retrograde transport of CI‐M6PR and the maintenance of lysosomal activity

Abstract

GCC88 is a golgin coiled-coil protein at the trans-Golgi (TGN) that functions as a tethering factor for the endosome-derived retrograde transport vesicles. Here, we demonstrate that GCC88 is required for the endosome-to-TGN retrograde transport of the cation-independent mannose 6-phosphate receptor (CI-M6PR). The knockout of GCC88 perturbs the retrieval of CI-M6PR and decreases its cellular level at the steady state, which causes the improper processing of newly synthesized cathepsin-D, a lysosomal hydrolase dependent on CI-M6PR for its delivery to lysosomes. At the whole cell level, the knockout of GCC88 reduces the lysosomal proteolytic capacity but does not impair of the efficiency of autophagy within these cells.

Getting Sugar Coating Right! The Role of the Golgi Trafficking Machinery in Glycosylation

“…GCC1 (GCC88): This GRIP-domain containing TGN localized Golgin is involved in endosome to Golgi retrograde transport [ 101 ] and maintains the tubular organization of the TGN [ 102 , 103 ]. GCC88 KD in HeLa cells led to mislocalization of the Qc SNARE syntaxin 6 which prevented the recycling of TGN38 and CI-M6PR from endosomes to the TGN [ 101 ].…”

“…GCC88 KD in HeLa cells led to mislocalization of the Qc SNARE syntaxin 6 which prevented the recycling of TGN38 and CI-M6PR from endosomes to the TGN [ 101 ]. Due to impaired CI-M6PR recycling, lysosomal activity was perturbed and the lysosomal enzyme Cathepsin D’s processing was impaired [ 103 ].…”