title: Loss of Dictyostelium ATG9 results in a pleiotropic phenotype affecting growth, development, phagocytosis and clearance and replication of Legionella pneumophila.
abstract: Infection of Dictyostelium discoideum with Legionella pneumophila resulted in a large number of differentially regulated genes among them three core autophagy genes, ATG8, ATG9 and ATG16. Macroautophagy contributes to many physiological and pathological processes and might also constitute an important mechanism in cell-autonomous immunity. For further studies we selected the highly conserved ATG9. In colocalization studies with GFP-tagged ATG9 and different organelle marker proteins we neither observed colocalization with mitochondria, the ER nor lysosomes. However, there was partial colocalization with the Golgi apparatus and many ATG9-GFP-containing vesicles localized along microtubules and accumulated around the microtubule organizing centre. ATG9-deficient cells had pleiotropic defects. In addition to growth defects they displayed severe developmental defects, consistent with the known role of autophagy in Dictyostelium development. Unexpectedly, the ATG9 mutant also had a strong phagocytosis defect that was particularly apparent when infecting the cells with L. pneumophila. However, those Legionellae that entered the host could multiply better in mutant than in wild-type cells, because of a less efficient clearance in the early and a more efficient replication in the late phase of infection. We conclude that ATG9 and hence macroautophagy has a protective role during pathogen infection.
authors.affiliation: Zentrum für Biochemie, Universität zu Köln, Germany.
authors.forename: Sze Man
authors.initials: SM
authors.lastname: Tung
authors.forename: Can
authors.initials: C
authors.lastname: Unal
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ley
authors.forename: Cohue
authors.initials: C
authors.lastname: Peña
authors.forename: Budi
authors.initials: B
authors.lastname: Tunggal
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
authors.forename: Oleg
authors.initials: O
authors.lastname: Krut
authors.forename: Michael
authors.initials: M
authors.lastname: Steinert
authors.forename: Ludwig
authors.initials: L
authors.lastname: Eichinger
mesh_terms: D004023:Dictyostelium / Q000235:genetics* / Q000254:growth & development / Q000276:immunology / Q000382:microbiology; D055786:Gene Knockout Techniques; D006056:Golgi Apparatus / Q000737:chemistry; D016952:Legionella pneumophila / Q000254:growth & development*; D008870:Microtubules / Q000737:chemistry; D010587:Phagocytosis; D015800:Protozoan Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology
chemical_list: D015800:Protozoan Proteins