The phenotypes of ATG9, ATG16 and ATG9/16 knock-out mutants imply autophagy-dependent and -independent functions |
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Authors: | Qiuhong Xiong Can ünal Jan Matthias Michael Steinert Ludwig Eichinger |
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Affiliation: | 1.Zentrum für Biochemie, Medizinische Fakultät, Universität zu Köln, Joseph-Stelzmann-Strasse 52, Köln 50931, Germany;2.Institut für Mikrobiologie, Technische Universität Braunschweig, Spielmannstrasse 7, Braunschweig 38106, Germany;3.Fen Fakültesi, Türk-Alman-Üniversitesi, Istanbul 34820, Turkey;4.Helmholtz Centre for Infection Research, Braunschweig 38124, Germany |
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Abstract: | Macroautophagy is a highly conserved intracellular bulk degradation system of all eukaryotic cells. It is governed by a large number of autophagy proteins (ATGs) and is crucial for many cellular processes. Here, we describe the phenotypes of Dictyostelium discoideum ATG16− and ATG9−/16− cells and compare them to the previously reported ATG9− mutant. ATG16 deficiency caused an increase in the expression of several core autophagy genes, among them atg9 and the two atg8 paralogues. The single and double ATG9 and ATG16 knock-out mutants had complex phenotypes and displayed severe and comparable defects in pinocytosis and phagocytosis. Uptake of Legionella pneumophila was reduced. In addition, ATG9− and ATG16− cells had dramatic defects in autophagy, development and proteasomal activity which were much more severe in the ATG9−/16− double mutant. Mutant cells showed an increase in poly-ubiquitinated proteins and contained large ubiquitin-positive protein aggregates which partially co-localized with ATG16-GFP in ATG9−/16− cells. The more severe autophagic, developmental and proteasomal phenotypes of ATG9−/16− cells imply that ATG9 and ATG16 probably function in parallel in autophagy and have in addition autophagy-independent functions in further cellular processes. |
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Keywords: | Dictyostelium autophagy development phagocytosis proteasome protein aggregate |
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