Universität zu Köln

Frumkin, Anna, Dror, Shiran, Pokrzywa, Wojciech ORCID: 0000-0002-5110-4462, Bar-Lavan, Yael, Karady, Ido, Hoppe, Thorsten ORCID: 0000-0002-4734-9352 and Ben-Zvi, Anat (2014). Challenging muscle homeostasis uncovers novel chaperone interactions in Caenorhabditis elegans. Front. Mol. Biosci., 1. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2296-889X

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Abstract

Proteome stability is central to cellular function and the lifespan of an organism. This is apparent in muscle cells, where incorrect folding and assembly of the sarcomere contributes to disease and aging. Apart from the myosin-assembly factor UNC-45, the complete network of chaperones involved in assembly and maintenance of muscle tissue is currently unknown. To identify additional factors required for sarcomere quality control, we performed genetic screens based on suppressed or synthetic motility defects in Caenorhabditis elegans. In addition to ethyl methyl sulfonate-based mutagenesis, we employed RNAi-mediated knockdown of candidate chaperones in unc-45 temperature-sensitive mutants and screened for impaired movement at permissive conditions. This approach confirmed the cooperation between UNC-45 and Hsp90. Moreover, the screens identified three novel co-chaperones, CeHop (STI-1), CeAha1 (C01G10.8) and Cep23 (ZC395.10), required for muscle integrity. The specific identification of Hsp90 and Hsp90 co-chaperones highlights the physiological role of Hsp90 in myosin folding. Our work thus provides a clear example of how a combination of mild perturbations to the proteostasis network can uncover specific quality control modules.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Frumkin, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Dror, Shiran UNSPECIFIED UNSPECIFIED UNSPECIFIED Pokrzywa, Wojciech UNSPECIFIED orcid.org/0000-0002-5110-4462 UNSPECIFIED Bar-Lavan, Yael UNSPECIFIED UNSPECIFIED UNSPECIFIED Karady, Ido UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED Ben-Zvi, Anat UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-423572
DOI:	10.3389/fmolb.2014.00021
Journal or Publication Title:	Front. Mol. Biosci.
Volume:	1
Date:	2014
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	2296-889X
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/42357