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The Nesprin-1/-2 ortholog ANC-1 regulates organelle positioning in C. elegans without its KASH or actin-binding domains

Hongyan Hao, Shilpi Kalra, Laura E. Jameson, Leslie A. Guerrero, View ORCID ProfileNatalie E. Cain, Jessica Bolivar, View ORCID ProfileDaniel A. Starr
doi: https://doi.org/10.1101/2020.07.14.202838
Hongyan Hao
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA
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Shilpi Kalra
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA
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Laura E. Jameson
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA
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Leslie A. Guerrero
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA
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Natalie E. Cain
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA
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  • ORCID record for Natalie E. Cain
Jessica Bolivar
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA
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Daniel A. Starr
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA
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  • For correspondence: dastarr@ucdavis.edu
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Abstract

KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of LINC complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the trans-membrane span. In anc-1 mutants, the ER was unanchored, moving throughout the cytoplasm, and often fragmented. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and likely other organelles in place.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Update author list, add Supplemental Figure 2, supplemental movie 3, and a few typos

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 25, 2020.
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The Nesprin-1/-2 ortholog ANC-1 regulates organelle positioning in C. elegans without its KASH or actin-binding domains
Hongyan Hao, Shilpi Kalra, Laura E. Jameson, Leslie A. Guerrero, Natalie E. Cain, Jessica Bolivar, Daniel A. Starr
bioRxiv 2020.07.14.202838; doi: https://doi.org/10.1101/2020.07.14.202838
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The Nesprin-1/-2 ortholog ANC-1 regulates organelle positioning in C. elegans without its KASH or actin-binding domains
Hongyan Hao, Shilpi Kalra, Laura E. Jameson, Leslie A. Guerrero, Natalie E. Cain, Jessica Bolivar, Daniel A. Starr
bioRxiv 2020.07.14.202838; doi: https://doi.org/10.1101/2020.07.14.202838

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