The yeast LYST homolog Bph1 is a Rab5 effector and prevents Atg8 lipidation at endosomes

Autor(en): Duarte, Prado Vargas
Hardenberg, Ralph
Mari, Muriel
Walter, Stefan
Reggiori, Fulvio
Froehlich, Florian 
Montoro, Ayelen Gonzalez
Ungermann, Christian 
Stichwörter: Atg8; Autophagy; BEACH-DOMAIN; BIOGENESIS; Bph1; Cell Biology; COMPLEX; ENDOCYTOSIS; Endosome; GTP-BINDING PROTEIN; LYSOSOME; LYST; MATURATION; MUTANTS; Rab5; SACCHAROMYCES-CEREVISIAE; VACUOLAR; Ypt52
Erscheinungsdatum: 2022
Herausgeber: COMPANY BIOLOGISTS LTD
Enthalten in: JOURNAL OF CELL SCIENCE
Band: 135
Ausgabe: 8
Zusammenfassung: 
Lysosomes mediate degradation of macromolecules to their precursors for cellular recycling. Additionally, lysosome-related organelles mediate cell type-specific functions. Chediak-Higashi syndrome is an autosomal, recessive disease, in which loss of the protein LYST causes defects in lysosomes and lysosome-related organelles. The molecular function of LYST, however, is largely unknown. Here, we dissected the function of the yeast LYST homolog, Bph1. We show that Bph1 is an endosomal protein and an effector of the minor Rab5 isoform Ypt52. Strikingly, bph1 Delta mutant cells have lipidated Atg8 on their endosomes, which is sorted via late endosomes into the vacuole lumen under non-autophagy-inducing conditions. In agreement with this, proteomic analysis of bph16, vacuoles reveals an accumulation of Atg8, reduced flux via selective autophagy, and defective endocytosis. Additionally, bph1 Delta cells have reduced autophagic flux under starvation conditions. Our observations suggest that Bph1 is a novel Rab5 effector that maintains endosomal functioning. When Bph1 is lost, Atg8 is lipidated at endosomes even during normal growth and ends up in the vacuole lumen. Thus, our results contribute to the understanding of the role of LYST-related proteins and associated diseases.
ISSN: 0021-9533
DOI: 10.1242/jcs.259421

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