Abstract
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.
Highlights
The intracellular transport of molecules between membrane-bound compartments ensures the current distribution of both proteins and lipids in cells
The molecular link between PtdIns(3)P and small GTPases is strengthened by the evidence that Rab5 is a master regulator of the PI3K enzymes responsible for phosphoinositide generation on endosomal membranes
Rab11 was found to direct Transferrin receptor sorting at the early endosome through regulation of the PtdIns(3)P level [148,149]
Summary
The intracellular transport of molecules between membrane-bound compartments ensures the current distribution of both proteins and lipids in cells. The redirection of membrane cargoes in response to environmental cues it is a well-recognized feature of membrane sorting, as exemplified by the Na,K-ATPase, an enzyme that controls ion gradients across cellular membranes This ion pump is considered a canonical basolateral protein, it localizes to the apical side of retinal pigment epithelium cells while other standard trafficking markers retain their characteristic distributions [10,11,12,13,14,15,16,17]. EGFR shifts between degradation and recycling in response to decreased affinity and concentration of ligands [18,19] Despite this evidence, it is less understood whether the distribution of other commonly studied cargoes is subjected to control by either a certain ligand, cell type, or cell status. The majority of studies add little to our knowledge of mechanisms that deal with the complex and repetitive processes required to sort molecules in cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
