Membrane-associated cargo recycling by tubule-based endosomal sorting

Abstract

The endosome system is a collection of organelles that sort membrane-associated proteins and lipids for lysosomal degradation or recycling back to their target organelle. Recycling cargo is captured in a network of membrane tubules emanating from endosomes where tubular carriers pinch off. These tubules are formed and stabilized through the scaffolding properties of cytosolic Bin/Amphiphysin/Rvs (BAR) proteins that comprise phosphoinositide-detecting moieties, recruiting these proteins to specific endosomal membrane areas. These include the protein family of sorting nexins that remodel endosome membrane into tubules by an evolutionary conserved mechanism of dimerization, local membrane curvature detection/induction and oligomerization. How the formation of such a tubular membrane carrier is coordinated with cargo capture is largely unknown. The tubular structure of the membrane carriers could sequester membrane-bound cargo through an iterative mechanism of geometric sorting. Furthermore, the recent identification of cargo adaptors for the endosome protein sorting complex retromer has expanded the sorting signals that retrieve specific sets of cargo away from lysosomal degradation through distinct membrane trafficking pathways.

Keywords: Amphipathic helix; BAR; Retromer; Sorting nexin.