Deliver on Time or Pay the Fine: Scheduling in Membrane Trafficking.

Membrane trafficking is all about time. Automation in such a biological process is crucial to ensure management and delivery of cellular cargoes with spatiotemporal precision. Shared molecular regulators and differential engagement of trafficking components improve robustness of molecular sorting. Sequential recruitment of low affinity protein complexes ensures directionality of the process and, concomitantly, serves as a kinetic proofreading mechanism to discriminate cargoes from the whole endocytosed material. This strategy helps cells to minimize losses and operating errors in membrane trafficking, thereby matching the appealed deadline. Here, we summarize the molecular pathways of molecular sorting, focusing on their timing and efficacy. We also highlight experimental procedures and genetic approaches to robustly probe these pathways, in order to guide mechanistic studies at the interface between biochemistry and quantitative biology.