FIGURE 12.

Model of altered intracellular membrane trafficking in COG depleted cells. In normal cells (A), the balance between the anterograde and retrograde trafficking ensures maintenance of compartment identity and proper trafficking of secretory cargo. Once secretory cargo reaches the end of the Golgi, it undergoes sorting and packaging into vesicles targeted to appropriate compartments. Endosomes containing endocytic cargo go thorough different stages of endosomal maturation and become late endosomes. Cargo form late endosomes is delivered to the Golgi. The GARP complex tethers late endosomes to the TGN. Golgi resident proteins and enzymes such as glycosyltransferases that get packaged along with secretory cargo are cycled back to the Golgi from late endosomes. Additionally, late endosomes also deliver lysosomal proteases and cargo destined for degradation to lysosomes. (B) When any individual COG subunit is knocked out, the COG complex is non-functional consequently affecting retrograde trafficking at the Golgi. However, the active GAPR complex, tethers late endosomes to the TGN feeding it with cargo and membrane. This results in a bottle neck effect at the TGN and the consequent enlargement of this compartment manifests as EELSs. Hence, when the GAPR complex is no longer active in COG4 KO cells, the EELSs are no longer formed. This figure was made using BioRender.