Sorting of cargo in the tubular endosomal network

Abstract

Intercellular communication is an essential process in all multicellular organisms. During this process, molecules secreted by one cell will bind to a receptor on the cognate cell leading to the subsequent uptake of the receptor-ligand complex. Once inside, the cell then determines the fate of the receptor-ligand complex and any other proteins that were endocytosed together. Approximately 80% of endocytosed material is recycled back to the plasma membrane either directly or indirectly via the Golgi apparatus and the remaining 20% is delivered to the lysosome for degradation. Although most pathways have been identified, we still lack understanding on how specificity in sorting of recycling cargos into different pathways is achieved, and how the cell reaches high accuracy of these processes in the absence of clear sorting signals in the bulk of the client proteins. In this review, we will summarize our current understanding of the mechanism behind recycling cargo sorting and propose a model of differential affinities between cargo and cargo receptors/adaptors with regards to iterative sorting in endosomes.

Multi-functional ARF1 compartments serve as a hub for short-range cargo transfer to endosomes

“…Sorting machinery (AP-1, clathrin) is located at the interface where the two membranes interact and would facilitate cargo enrichment and transfer during kiss-and-run. Advancing previous thinking in this field, our findings suggest a model where cargo sorting would be mediated by a tubular network connecting the trans-Golgi network (TGN) with endo-lysosomes and the plasma membrane 13,[33][34][35] .…”

“…First described in neurons 12 , kiss-and-run events enable organelles to exchange material through transient pore formation, yet the involved compartments retain their identity, and putative diffusion barriers would avoid lipid and content mixing. Material exchange between organelles in a kiss-and-run fashion would require direct organelle interaction and the presence of a tubular endosomal network where endosomal compartments could closely interact 13 . Various secretory and endocytic recycling cargoes were found to traffic via tubulo-vesicular compartments [14][15][16][17][18] , some of which were decorated with clathrin [19][20][21] .…”

Syndapin Regulates the RAP-1 GTPase to Control Endocytic Recycling via RHO-1 and Non-Muscle Myosin II

“…Uptake mechanisms can be generally divided into clathrin-dependent and clathrin-independent endocytosis (CDE and CIE, respectively), after which internalized cargo is sorted within endosomes for delivery to distinct intracellular destinations (2). As membrane and fluid are added to the early endosome by incoming vesicles, narrow-diameter recycling tubules form, collecting a subset of cargo (3). Most plasma membrane lipids, and many types of internalized transmembrane proteins, are recycled back to the plasma membrane either directly (rapid recycling), indirectly via the endocytic recycling compartment (ERC) (slow recycling), or Golgi (retrograde recycling) (3, 4).…”

“…As membrane and fluid are added to the early endosome by incoming vesicles, narrow-diameter recycling tubules form, collecting a subset of cargo (3). Most plasma membrane lipids, and many types of internalized transmembrane proteins, are recycled back to the plasma membrane either directly (rapid recycling), indirectly via the endocytic recycling compartment (ERC) (slow recycling), or Golgi (retrograde recycling) (3, 4). As early endosomes mature they become late endosomes, eventually fusing with lysosomes, promoting degradation of remaining cargo.…”

“…As early endosomes mature they become late endosomes, eventually fusing with lysosomes, promoting degradation of remaining cargo. Many cellular processes depend upon accurate and efficient endocytic recycling, including cell migration, cell division, cell-cell fusion events, and control of neuronal signaling during learning and memory (3, 4). Trafficking pathways are often more elaborate in the context of polarized cells such as epithelia and neurons that maintain multiple functionally distinct plasma membrane domains, e.g.…”