Universität zu Köln

Karow, Malte, Fischer, Sarah, Messling, Susanne, Konertz, Roman ORCID: 0000-0002-6488-1885, Riehl, Jana, Xiong, Qiuhong, Rijal, Ramesh ORCID: 0000-0003-0498-1064, Wagle, Prerana, Clemen, Christoph S. and Eichinger, Ludwig ORCID: 0000-0003-1594-6117 (2020). Functional Characterisation of the Autophagy ATG12 similar to 5/16 Complex in Dictyostelium discoideum. Cells, 9 (5). BASEL: MDPI. ISSN 2073-4409

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Abstract

Macroautophagy, a highly conserved and complex intracellular degradative pathway, involves more than 20 core autophagy (ATG) proteins, among them the hexameric ATG12 similar to 5/16 complex, which is part of the essential ubiquitin-like conjugation systems in autophagy. Dictyostelium discoideum atg5 single, atg5/12 double, and atg5/12/16 triple gene knock-out mutant strains displayed similar defects in the conjugation of ATG8 to phosphatidylethanolamine, development, and cell viability upon nitrogen starvation. This implies that ATG5, 12 and 16 act as a functional unit in canonical autophagy. Macropinocytosis of TRITC dextran and phagocytosis of yeast were significantly decreased in ATG5(-) and ATG5(-)/12(-) and even further in ATG5(-)/12(-)/16(-) cells. In contrast, plaque growth on Klebsiella aerogenes was about twice as fast for ATG5(-) and ATG5(-)/12(-)/16(-) cells in comparison to AX2, but strongly decreased for ATG5(-)/12(-) cells. Along this line, phagocytic uptake of Escherichia coli was significantly reduced in ATG5(-)/12(-) cells, while no difference in uptake, but a strong increase in membrane association of E. coli, was seen for ATG5(-) and ATG5(-)/12(-)/16(-) cells. Proteasomal activity was also disturbed in a complex fashion, consistent with an inhibitory activity of ATG16 in the absence of ATG5 and/or ATG12. Our results confirm the essential function of the ATG12 similar to 5/16 complex in canonical autophagy, and furthermore are consistent with autophagy-independent functions of the complex and its individual components. They also strongly support the placement of autophagy upstream of the ubiquitin-proteasome system (UPS), as a fully functional UPS depends on autophagy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Karow, Malte UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Messling, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Konertz, Roman UNSPECIFIED orcid.org/0000-0002-6488-1885 UNSPECIFIED Riehl, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Xiong, Qiuhong UNSPECIFIED UNSPECIFIED UNSPECIFIED Rijal, Ramesh UNSPECIFIED orcid.org/0000-0003-0498-1064 UNSPECIFIED Wagle, Prerana UNSPECIFIED UNSPECIFIED UNSPECIFIED Clemen, Christoph S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichinger, Ludwig UNSPECIFIED orcid.org/0000-0003-1594-6117 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-334937
DOI:	10.3390/cells9051179
Journal or Publication Title:	Cells
Volume:	9
Number:	5
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language UBIQUITIN-PROTEASOME SYSTEM; SLIME-MOLD; ENDOPLASMIC-RETICULUM; CONJUGATION SYSTEM; MEMBRANE-BINDING; LC3 LIPIDATION; 8 PROTEINS; DEGRADATION; DISEASE; MODEL Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33493