Retromer Is Required for Apoptotic Cell Clearance by Phagocytic Receptor Recycling

Abstract

The cell surface receptor CED-1 mediates apoptotic cell recognition by phagocytic cells, enabling cell corpse clearance in Caenorhabditis elegans. Here, we found that the C. elegans intracellular protein sorting complex, retromer, was required for cell corpse clearance by mediating the recycling of CED-1. Retromer was recruited to the surfaces of phagosomes containing cell corpses, and its loss of function caused defective cell corpse removal. The retromer probably acted through direct interaction with CED-1 in the cell corpse recognition pathway. In the absence of retromer function, CED-1 associated with lysosomes and failed to recycle from phagosomes and cytosol to the plasma membrane. Thus, retromer is an essential mediator of apoptotic cell clearance by regulating phagocytic receptor(s) during cell corpse engulfment.

TLR-dependent phagosome tubulation in dendritic cells promotes phagosome cross-talk to optimize MHC-II antigen presentation

“…S1A). Thus, long phagotubules are prominent features of phagosomes at a late stage of maturation in DCs, and are distinguishable from the tubules that emanate from macrophage phagosomes early after phagocytosis (21,22).…”

“…Phagosomal TLR signaling has been proposed to also promote the reorganization of phagosome-derived MHC-II-enriched compartments (MIICs) to favor the delivery of MHC-II-peptide complexes to the plasma membrane (17), analogous to TLR-stimulated formation of tubules from MIICs/lysosomes (18)(19)(20) that fuse with the plasma membrane (7) and extend toward the immunologic synapse with T cells (5). Tubules emerge from phagosomes in macrophages shortly after phagocytosis and likely function in membrane recycling during early phagosome maturation stages (21)(22)(23), but tubules at later stages that might facilitate the presentation of phagosome-derived MHC-II-peptide complexes have not been reported previously. Moreover, a role for TLR signaling in formation of phagosome-derived tubules has not been established.…”

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

“…The Dictyostelium Sibs and the macrophage integrin-like phagocytic receptors are therefore likely to be sorted in a similar manner. Other phagocytic receptors, such as the Caenorhabditis elegans apoptotic corpse receptor CED-1, are recycled from phagosomes in a retromer-dependent manner (63). Therefore, both retromer-dependent and -independent sorting are likely to occur simultaneously.…”

Retromer Contributes to Immunity-Associated Cell Death in Arabidopsis

“…In yeast and mammalian cells, retromer binds specific peptide motifs in vacuolar and lysosomal acid hydrolase receptors, respectively, and mediates their recycling from endosomes back to the TGN (Nothwehr et al, 2000;Seaman, 2007;Bonifacino and Hurley, 2008). In addition, retromer-mediated protein sorting has been shown for a range of other transmembrane receptors and revealed retromer functions in processes such as Wntdependent signaling, apoptotic cell clearance, and the prevention of neurodegenerative diseases (Port et al, 2008;Chen et al, 2010;Lane et al, 2012). In plants, retromer components have been implicated in recycling vacuolar sorting receptors (Oliviusson et al, 2006;Kang et al, 2012) and in the vacuolar trafficking of plasma membrane proteins such as PIN-FORMED auxin efflux carriers (Kleine-Vehn et al, 2008;Nodzynski et al, 2013).…”