Assembly and fission of tubular carriers mediating protein sorting in endosomes

Abstract

Endosomes are central protein-sorting stations at the crossroads of numerous membrane trafficking pathways in all eukaryotes. They have a key role in protein homeostasis and cellular signalling and are involved in the pathogenesis of numerous diseases. Endosome-associated protein assemblies or coats collect transmembrane cargo proteins and concentrate them into retrieval domains. These domains can extend into tubular carriers, which then pinch off from the endosomal membrane and deliver the cargoes to appropriate subcellular compartments. Here we discuss novel insights into the structure of a number of tubular membrane coats that mediate the recruitment of cargoes into these carriers, focusing on sorting nexin-based coats such as Retromer, Commander and ESCPE-1. We summarize current and emerging views of how selective tubular endosomal carriers form and detach from endosomes by fission, highlighting structural aspects, conceptual challenges and open questions. Endosomes function as sorting stations that segregate cargo proteins into endosomal carriers, enabling their distribution to subcellular target compartments. Increasingly detailed structural insights have revealed how proteins, such as sorting nexins, assemble on endosomal membranes to form a coat that facilitates the formation and detachment of tubular carriers.