Two-dimensional HRS condensates drive the assembly of flat clathrin lattices on endosomes
A study published in Nature Communications reveals that the ESCRT-0 protein HRS undergoes two-dimensional phase separation on endosomal membranes, forming gel-like condensates. These condensates recruit clathrin to assemble multilayered, flat coats, a structure distinct from the curved clathrin lattices involved in vesicle budding. The research demonstrates that this process occurs spontaneously at physiological HRS concentrations below 50 nM. Using correlative cryo-electron tomography, the team observed these multilayered structures in cells, with flat clathrin layers positioned approximately 16 nm from the membrane. Cholesterol plays a critical role by enhancing HRS recruitment and promoting phase separation, creating a positive feedback loop that concentrates cholesterol and forms stable microdomains for sorting ubiquitinated cargoes. This findings provide new insights into the molecular mechanisms governing cargo sorting and membrane organization within endosomes, highlighting the importance of supramolecular assembly and lipid-protein interactions in cellular trafficking.
Wire timeline
Two-dimensional HRS condensates drive the assembly of flat clathrin lattices on endosomes
A study published in Nature Communications reveals that the ESCRT-0 protein HRS undergoes two-dimensional phase separation on endosomal membranes, forming gel-like condensates. These condensates recruit clathrin to assemble multilayered, flat coats, a structure distinct from the curved clathrin lattices involved in vesicle budding. The research demonstrates that this process occurs spontaneously at physiological HRS concentrations below 50 nM. Using correlative cryo-electron tomography, the team observed these multilayered structures in cells, with flat clathrin layers positioned approximately 16 nm from the membrane. Cholesterol plays a critical role by enhancing HRS recruitment and promoting phase separation, creating a positive feedback loop that concentrates cholesterol and forms stable microdomains for sorting ubiquitinated cargoes. This findings provide new insights into the molecular mechanisms governing cargo sorting and membrane organization within endosomes, highlighting the importance of supramolecular assembly and lipid-protein interactions in cellular trafficking.
Nature Communications