Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles
Efficient 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 re...
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Elsevier
2024-06-01
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Series: | European Journal of Cell Biology |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933524000281 |
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author | Rebecca Holzapfel Agata Prell Fabian Schumacher Veronika Perschin José Pedro Friedmann Angeli Burkhard Kleuser Christian Stigloher Gholamreza Fazeli |
author_facet | Rebecca Holzapfel Agata Prell Fabian Schumacher Veronika Perschin José Pedro Friedmann Angeli Burkhard Kleuser Christian Stigloher Gholamreza Fazeli |
author_sort | Rebecca Holzapfel |
collection | DOAJ |
description | Efficient 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 phagolysosomes over time, we identified a role of prosaposin/SPP-10 in maintaining phagolysosomal structure, which promotes efficient resolution of phagocytic cargos. |
first_indexed | 2024-04-24T12:47:23Z |
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institution | Directory Open Access Journal |
issn | 0171-9335 |
language | English |
last_indexed | 2024-04-24T12:47:23Z |
publishDate | 2024-06-01 |
publisher | Elsevier |
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series | European Journal of Cell Biology |
spelling | doaj.art-f1277601255b4e6fb89dac0dced323cc2024-04-07T04:35:12ZengElsevierEuropean Journal of Cell Biology0171-93352024-06-011032151411Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesiclesRebecca Holzapfel0Agata Prell1Fabian Schumacher2Veronika Perschin3José Pedro Friedmann Angeli4Burkhard Kleuser5Christian Stigloher6Gholamreza Fazeli7Imaging Core Facility, Biocenter, University of Würzburg, Würzburg, GermanyInstitute of Pharmacy, Freie Universität Berlin, Berlin, GermanyInstitute of Pharmacy, Freie Universität Berlin, Berlin, Germany; Core-Facility BioSupraMol, Pharma-MS subunit, Freie Universität Berlin, GermanyImaging Core Facility, Biocenter, University of Würzburg, Würzburg, GermanyChair of Translational Cell Biology, Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, GermanyInstitute of Pharmacy, Freie Universität Berlin, Berlin, GermanyImaging Core Facility, Biocenter, University of Würzburg, Würzburg, GermanyChair of Translational Cell Biology, Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany; Corresponding author.Efficient 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 phagolysosomes over time, we identified a role of prosaposin/SPP-10 in maintaining phagolysosomal structure, which promotes efficient resolution of phagocytic cargos.http://www.sciencedirect.com/science/article/pii/S0171933524000281Phagolysosome resolutionCell corpse clearanceLysosomeSphingolipidomeHexosylceramidesGlucosyl ceramidases |
spellingShingle | Rebecca Holzapfel Agata Prell Fabian Schumacher Veronika Perschin José Pedro Friedmann Angeli Burkhard Kleuser Christian Stigloher Gholamreza Fazeli Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles European Journal of Cell Biology Phagolysosome resolution Cell corpse clearance Lysosome Sphingolipidome Hexosylceramides Glucosyl ceramidases |
title | Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles |
title_full | Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles |
title_fullStr | Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles |
title_full_unstemmed | Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles |
title_short | Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles |
title_sort | degradation of hexosylceramides is required for timely corpse clearance via formation of cargo containing phagolysosomal vesicles |
topic | Phagolysosome resolution Cell corpse clearance Lysosome Sphingolipidome Hexosylceramides Glucosyl ceramidases |
url | http://www.sciencedirect.com/science/article/pii/S0171933524000281 |
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