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Lim et al. investigate the internalization mechanism of the antigen presenting molecule, MR1. Recognition of a conserved atypical motif in MR1’s cytoplasmic tail by AP2 defines the endocytosis rate and duration of MR1–metabolite cell surface display, functioning as the “off” switch for MR1 presentation.

Exosomes are derived from endosomal compartments with an ill-defined molecular identity and whose trafficking steps to secretion are poorly understood. Using advanced imaging approaches, the authors identified these compartments as pre-lysosomal endosomes that require dynamic membrane contact sites with the endoplasmic reticulum to induce a prosecretory cascade of small-GTPases.

To sense potential mating partners’ positions, yeast uses a default polarity site to assemble a gradient tracking machine (GTM), which redistributes up the pheromone gradient. Here, Wang et al. show that GTM redistribution requires default-site inactivation and actin-independent vesicle delivery.

The biogenesis of secretory granules (SGs) is poorly understood. Here, we show that chromogranin proteins form a liquid scaffold upon entry into the milieu of the trans-Golgi network (TGN). These scaffolds recruit clients such as proinsulin and facilitate their transport to SGs.

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