Dictyostelium lacking the single atlastin homolog Sey1 shows aberrant ER architecture, proteolytic processes and expansion of the Legionella‐containing vacuole. (24th February 2021)

• Record Type: Journal Article
• Authors: Hüsler, Dario; Steiner, Bernhard; Welin, Amanda; Striednig, Bianca; Swart, A. Leoni; Molle, Virginie; Hilbi, Hubert; Letourneur, François
• Is Part Of: Cellular microbiology. Volume 23:Number 5(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-02-24
• Subjects: amoeba -- atlastin -- Dictyostelium discoideum -- endocytic pathway -- host‐pathogen interaction -- large GTPase -- Legionella pneumophila -- Legionnaires' disease -- pathogen vacuole -- unfolded protein response; Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.13318
• Languages: English
• ISSNs: 1462-5814

Abstract

Abstract: Dictyostelium discoideum Sey1 is the single ortholog of mammalian atlastin 1–3 (ATL1‐3), which are large homodimeric GTPases mediating homotypic fusion of endoplasmic reticulum (ER) tubules. In this study, we generated a D. discoideum mutant strain lacking the sey1 gene and found that amoebae deleted for sey1 are enlarged, but grow and develop similarly to the parental strain. The ∆ sey1 mutant amoebae showed an altered ER architecture, and the tubular ER network was partially disrupted without any major consequences for other organelles or the architecture of the secretory and endocytic pathways. Macropinocytic and phagocytic functions were preserved; however, the mutant amoebae exhibited cumulative defects in lysosomal enzymes exocytosis, intracellular proteolysis, and cell motility, resulting in impaired growth on bacterial lawns. Moreover, ∆ sey1 mutant cells showed a constitutive activation of the unfolded protein response pathway (UPR), but they still readily adapted to moderate levels of ER stress, while unable to cope with prolonged stress. In D. discoideum ∆ sey1 the formation of the ER‐associated compartment harbouring the bacterial pathogen Legionella pneumophila was also impaired. In the mutant amoebae, the ER was less efficiently recruited to the " Legionella ‐containing vacuole" (LCV), the expansion of the pathogen vacuole was inhibited at early stages of infection and intracellular bacterial growth was reduced. In summary, our study establishes a role of D. discoideum Sey1 in ER architecture, proteolysis, cell motility and intracellular replication of L. pneumophila . Abstract : Dictyostelium discoideum Sey1 is the single ortholog of mammalian atlastin 1‐3, which are large homodimeric GTPases mediating fusion of tubular endoplasmic reticulum (ER). Mutant amoebae lacking Sey1 grow and develop similarly to the parental strain, but show an aberrant ER architecture, defects in proteolytic processes and diminished cell motility. In ∆ sey1 amoebae, the recruitment of ER to the unique vacuole harboring the pathogen Legionella pneumophila is reduced, expansion of the ER‐associated vacuole is defective, and intracellular bacterial growth is impaired.