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Degradation of hexosylceramides is required for timely corpse clearance via formation of cargo-containing phagolysosomal vesicles.
Holzapfel, Rebecca; Prell, Agata; Schumacher, Fabian; Perschin, Veronika; Friedmann Angeli, José Pedro; Kleuser, Burkhard; Stigloher, Christian; Fazeli, Gholamreza.
Afiliación
  • Holzapfel R; Imaging Core Facility, Biocenter, University of Würzburg, Würzburg, Germany.
  • Prell A; Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
  • Schumacher F; Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany; Core-Facility BioSupraMol, Pharma-MS subunit, Freie Universität Berlin, Germany.
  • Perschin V; Imaging Core Facility, Biocenter, University of Würzburg, Würzburg, Germany.
  • Friedmann Angeli JP; Chair of Translational Cell Biology, Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany.
  • Kleuser B; Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
  • Stigloher C; Imaging Core Facility, Biocenter, University of Würzburg, Würzburg, Germany.
  • Fazeli G; Chair of Translational Cell Biology, Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany. Electronic address: gholamreza.fazeli@uni-wuerzburg.de.
Eur J Cell Biol ; 103(2): 151411, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38582051
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fagosomas / Caenorhabditis elegans / Proteínas de Caenorhabditis elegans Límite: Animals Idioma: En Revista: Eur J Cell Biol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fagosomas / Caenorhabditis elegans / Proteínas de Caenorhabditis elegans Límite: Animals Idioma: En Revista: Eur J Cell Biol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania