Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles

Eur J Cell Biol. 2024 Apr 5;103(2):151411. doi: 10.1016/j.ejcb.2024.151411. Online ahead of print.ABSTRACTEfficient degradation of phagocytic cargo in lysosomes is crucial to maintain cellular homeostasis and defending cells against pathogens. However, the mechanisms underlying the degradation and recycling of macromolecular cargo within the phagolysosome remain incompletely understood. We previously reported that the phagolysosome containing the corpse of the polar body in C. elegans tubulates into small vesicles to facilitate corpse clearance, a process that requires cargo protein degradation and amino acid export. Here we show that degradation of hexosylceramides by the prosaposin ortholog SPP-10 and glucosylceramidases is required for timely corpse clearance. We observed accumulation of membranous structures inside endolysosomes of spp-10-deficient worms, which are likely caused by increased hexosylceramide species. spp-10 deficiency also caused alteration of additional sphingolipid subclasses, like dihydroceramides, 2-OH-ceramides, and dihydrosphingomyelins. While corpse engulfment, initial breakdown of corpse membrane inside the phagolysosome and lumen acidification proceeded normally in spp-10-deficient worms, formation of the cargo-containing vesicles from the corpse phagolysosome was reduced, resulting in delayed cargo degradation and phagolysosome resolution. Thus, by combining ultrastructural studies and sphingolipidomic analysis with observing single phagolysosome...

Source: European Journal of Cell Biology - April 6, 2024 Category: Cytology Authors: Rebecca Holzapfel Agata Prell Fabian Schumacher Veronika Perschin Jos é Pedro Friedmann Angeli Burkhard Kleuser Christian Stigloher Gholamreza Fazeli Source Type: research