IST1 regulates select endosomal recycling pathways

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.31.551359v1?rss=1 Authors: Clippinger, A. K., Naismith, T. V., Yoo, W., Jansen, S., Kast, D., Hanson, P. I. Abstract: ESCRTs (Endosomal Sorting Complex Required for Transport) are a modular set of protein complexes with membrane remodeling activities that include the formation and release of intralumenal vesicles (ILVs) to generate multivesicular endosomes. While most of the 12 ESCRT-III proteins are known to play roles in ILV formation, IST1 has been associated with a wider range of endosomal remodeling events. Here, we extend previous studies of IST1 function in endosomal trafficking and establish that IST1, along with its binding partner CHMP1B, contributes to scission of early endosomal carriers. Functionally, depleting IST1 impairs delivery of transferrin receptor from early/sorting endosomes to the endocytic recycling compartment and instead increases its rapid recycling to the plasma membrane via peripheral endosomes enriched in the clathrin adaptor AP-1. IST1 is also important for export of mannose 6-phosphate receptor from early/sorting endosomes. Examination of IST1 binding partners on these endosomes revealed that IST1 interacts both with CHMP1B and with the MIT domain-containing sorting nexin SNX15 previously reported to regulate endosomal recycling. Kinetic and spatial analyses showed that SNX15 and IST1 occupy a clathrin-containing subdomain distinct from those previously connected to cargo retrieval or degradation. Using live-cell microscopy we demonstrate that SNX15 and CHMP1B alternately control recruitment of IST1 to this domain on the endosomal perimeter and the base of endosomal tubules. These findings indicate that IST1 plays an important and regulated role in specific recycling pathways from the early/sorting endosome. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC