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Leveraging a gain-of-function allele of Caenorhabditis elegans paqr-1 to elucidate membrane homeostasis by PAQR proteins


Autoři: Kiran Busayavalasa aff001;  Mario Ruiz aff001;  Ranjan Devkota aff001;  Marcus Ståhlman aff002;  Rakesh Bodhicharla aff001;  Emma Svensk aff001;  Nils-Olov Hermansson aff003;  Jan Borén aff002;  Marc Pilon aff001
Působiště autorů: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden aff001;  Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden aff002;  Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, Sweden aff003
Vyšlo v časopise: Leveraging a gain-of-function allele of Caenorhabditis elegans paqr-1 to elucidate membrane homeostasis by PAQR proteins. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008975
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008975

Souhrn

The C. elegans proteins PAQR-2 (a homolog of the human seven-transmembrane domain AdipoR1 and AdipoR2 proteins) and IGLR-2 (a homolog of the mammalian LRIG proteins characterized by a single transmembrane domain and the presence of immunoglobulin domains and leucine-rich repeats in their extracellular portion) form a complex that protects against plasma membrane rigidification by promoting the expression of fatty acid desaturases and the incorporation of polyunsaturated fatty acids into phospholipids, hence increasing membrane fluidity. In the present study, we leveraged a novel gain-of-function allele of PAQR-1, a PAQR-2 paralog, to carry out structure-function studies. We found that the transmembrane domains of PAQR-2 are responsible for its functional requirement for IGLR-2, that PAQR-1 does not require IGLR-2 but acts via the same pathway as PAQR-2, and that the divergent N-terminal cytoplasmic domains of the PAQR-1 and PAQR-2 proteins serve a regulatory function and may regulate access to the catalytic site of these proteins. We also show that overexpression of human AdipoR1 or AdipoR2 alone is sufficient to confer increased palmitic acid resistance in HEK293 cells, and thus act in a manner analogous to the PAQR-1 gain-of-function allele.

Klíčová slova:

Alleles – Caenorhabditis elegans – Cell membranes – Fluorescence recovery after photobleaching – Lipids – Membrane proteins – Phenotypes – Protein domains


Zdroje

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