Hepatic glycogenolysis is essential for protein glycosylation and rhythmic secretion by the liver. Disruptions to hepatic glycogenolysis, caused by congenital diseases or physiological factors such as...

The Retromer coat is conserved in all eukaryotes and is crucial for the correct intracellular sorting of many transmembrane receptors and lysosomal hydrolases. Retromer is an effector of the late endosomal small GTPase RAB7 and is also implicated in its inactivation required for proper endosomal maturation. Here, we explore the role of controlled GTP hydrolysis by the RAB7 ortholog Ypt7 in the formation of Retromer-coated membrane carriers in yeast. Proximity labelling and genetic ablation identify the GTPase Activating Protein (GAP) Gyp6 as a critical regulator of Ypt7 activity in the context or Retromer. Structural studies show that Retromer recruits Gyp6 through its Vps29 subunit, which recognises a specific PL motif and a secondary binding site in the C-terminal domain of Gyp6. This interaction does not occur with other yeast GAPs. Ablation of the Gyp6-Retromer interface or the catalytic activity of Gyp6 leads to the accumulation of tubular structures on endo-lysosomal compartments and to increased association of Ypt7 with Retromer and its cargo Vps10. These results support a model in which Gyp6 controls the switch from Ypt7-dependent Retromer coat assembly and cargo collection to the departure of the carrier through membrane fission and uncoating. ### Competing Interest Statement The authors have declared no competing interest. National Health and Medical Research Council, https://ror.org/011kf5r70, APP2016410 Swiss National Science Foundation, https://ror.org/00yjd3n13, 31003A_179306, 310030_204713, 10.006.083

Trans-endothelial transport of nanoparticles remains poorly characterized in live organisms. The zebrafish is a well-established model for direct in vivo imaging; however, standardized controls have n...

Targeted nanoparticles have the potential to revolutionize therapeutics for medical applications. Here, we demonstrate the utility of a flexible precision nanovesicle delivery system for functional de...

The Editor-in-Chief (EIC) of Journal of Cell Science plays a key role in defining the overall vision of the journal, helping to decide on journal strategy, policy and priorities, and overseeing all co...

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