Universität zu Köln

Kutzner, Carl Elias ORCID: 0000-0003-4053-2231, Bauer, Karen Carolyn ORCID: 0009-0003-2505-0549, Lackmann, Jan-Wilm ORCID: 0000-0001-8182-8034, Acton, Richard James ORCID: 0000-0002-2574-9611, Sarkar, Anwesha ORCID: 0000-0002-2150-9653, Pokrzywa, Wojciech ORCID: 0000-0002-5110-4462 and Hoppe, Thorsten ORCID: 0000-0002-4734-9352 (2024). Optogenetic induction of mechanical muscle stress identifies myosin regulatory ubiquitin ligase NHL-1 in C. elegans. Nature Communications, 15 (1). pp. 1-18. Springer Nature. ISSN 2041-1723

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Abstract

[Artikel-Nr.: 6879] Mechanical stress during muscle contraction is a constant threat to proteome integrity. However, there is a lack of experimental systems to identify critical proteostasis regulators under mechanical stress conditions. Here, we present the transgenic Caenorhabditis elegans model OptIMMuS (Optogenetic Induction of Mechanical Muscle Stress) to study changes in the proteostasis network associated with mechanical forces. Repeated blue light exposure of a muscle-expressed Chlamydomonas rheinhardii channelrhodopsin-2 variant results in sustained muscle contraction and mechanical stress. Using OptIMMuS, combined with proximity labeling and mass spectrometry, we identify regulators that cooperate with the myosin-directed chaperone UNC-45 in muscle proteostasis. One of these is the TRIM E3 ligase NHL-1, which interacts with UNC-45 and muscle myosin in genetic epistasis and co-immunoprecipitation experiments. We provide evidence that the ubiquitylation activity of NHL-1 regulates myosin levels and functionality under mechanical stress. In the future, OptIMMuS will help to identify muscle-specific proteostasis regulators of therapeutic relevance.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Kutzner, Carl Elias UNSPECIFIED https://orcid.org/0000-0003-4053-2231 UNSPECIFIED Bauer, Karen Carolyn UNSPECIFIED https://orcid.org/0009-0003-2505-0549 UNSPECIFIED Lackmann, Jan-Wilm UNSPECIFIED https://orcid.org/0000-0001-8182-8034 UNSPECIFIED Acton, Richard James UNSPECIFIED https://orcid.org/0000-0002-2574-9611 UNSPECIFIED Sarkar, Anwesha UNSPECIFIED https://orcid.org/0000-0002-2150-9653 UNSPECIFIED Pokrzywa, Wojciech UNSPECIFIED https://orcid.org/0000-0002-5110-4462 UNSPECIFIED Hoppe, Thorsten UNSPECIFIED https://orcid.org/0000-0002-4734-9352 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-814791
Identification Number:	10.1038/s41467-024-51069-3
Journal or Publication Title:	Nature Communications
Volume:	15
Number:	1
Page Range:	pp. 1-18
Number of Pages:	18
Date:	11 August 2024
Publisher:	Springer Nature
ISSN:	2041-1723
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics Zentrum für Molekulare Medizin
Subjects:	Life sciences Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81479