Decreased torsinA or LINC Complex Function Rescues a Laminopathy in Caenorhabditis elegans

The function of the nucleus depends on the integrity of the nuclear lamina, an intermediate filament network associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex spanning the nuclear envelope. In turn, the AAA+ ATPase torsinA regulates force transmission from the cytoskeleton...

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Published inbioRxiv
Main Authors Huelgas-Morales, Gabriela, Sanders, Mark, Gemechu Mekonnen, Tsukamoto, Tatsuya, Greenstein, David I
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 23.04.2020
Subjects
Adenosine triphosphatase
Aging
Cytoskeleton
Dystonia
Mutation
Myopathy
Nuclei
Progeria
Sterility
Worms
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Summary:The function of the nucleus depends on the integrity of the nuclear lamina, an intermediate filament network associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex spanning the nuclear envelope. In turn, the AAA+ ATPase torsinA regulates force transmission from the cytoskeleton to the nucleus. In humans, mutations affecting nuclear envelope-associated proteins cause laminopathies, including progeria, myopathy, and dystonia. We report that decreasing the function of the C. elegans torsinA homolog, OOC-5, rescues the sterility and premature aging caused by a null mutation in the single worm lamin homolog, lmn-1. Loss of OOC-5 activity prevents nuclear collapse in lmn-1 mutants by disrupting the function of the LINC complex. These results suggest that LINC complex-transmitted forces damage nuclei with a compromised nuclear lamina. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.04.22.055988