Universität zu Köln

Fischer, Sarah ORCID: 0000-0001-6227-3950, Rijal, Ramesh, Frommolt, Peter ORCID: 0000-0002-1966-8014, Wagle, Prerana, Konertz, Roman, Faix, Jan, Wissling, Susanne and Eichinger, Ludwig ORCID: 0000-0003-1594-6117 (2019). Functional Characterization of Ubiquitin-Like Core Autophagy Protein ATG12 in Dictyostelium discoideum. Cells, 8 (1). BASEL: MDPI. ISSN 2073-4409

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Abstract

Autophagy is a highly conserved intracellular degradative pathway that is crucial for cellular homeostasis. During autophagy, the core autophagy protein ATG12 plays, together with ATG5 and ATG16, an essential role in the expansion of the autophagosomal membrane. In this study we analyzed gene replacement mutants of atg12 in Dictyostelium discoideum AX2 wild-type and ATG16(-) cells. RNA(seq) analysis revealed a strong enrichment of, firstly, autophagy genes among the up-regulated genes and, secondly, genes implicated in cell motility and phagocytosis among the down-regulated genes in the generated ATG12(-), ATG16(-) and ATG12(-)/16(-) cells. The mutant strains showed similar defects in fruiting body formation, autolysosome maturation, and cellular viability, implying that ATG12 and ATG16 act as a functional unit in canonical autophagy. In contrast, ablation of ATG16 or of ATG12 and ATG16 resulted in slightly more severe defects in axenic growth, macropinocytosis, and protein homeostasis than ablation of only ATG12, suggesting that ATG16 fulfils an additional function in these processes. Phagocytosis of yeast, spore viability, and maximal cell density were much more affected in ATG12(-)/16(-) cells, indicating that both proteins also have cellular functions independent of each other. In summary, we show that ATG12 and ATG16 fulfil autophagy-independent functions in addition to their role in canonical autophagy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fischer, Sarah UNSPECIFIED orcid.org/0000-0001-6227-3950 UNSPECIFIED Rijal, Ramesh UNSPECIFIED UNSPECIFIED UNSPECIFIED Frommolt, Peter UNSPECIFIED orcid.org/0000-0002-1966-8014 UNSPECIFIED Wagle, Prerana UNSPECIFIED UNSPECIFIED UNSPECIFIED Konertz, Roman UNSPECIFIED UNSPECIFIED UNSPECIFIED Faix, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wissling, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichinger, Ludwig UNSPECIFIED orcid.org/0000-0003-1594-6117 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-139588
DOI:	10.3390/cells8010072
Journal or Publication Title:	Cells
Volume:	8
Number:	1
Date:	2019
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MULTICELLULAR DEVELOPMENT; PROTEASOMAL ACTIVITY; CONJUGATION SYSTEMS; LC3 LIPIDATION; DEGRADATION; PATHWAYS; CROSSTALK; DISEASE; COMPLEX; ACTIN Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13958