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PP2A:B56 Regulates Meiotic Chromosome Segregation in C. elegans Oocytes

View ORCID ProfileLaura Bel Borja, Flavie Soubigou, Samuel J.P. Taylor, Conchita Fraguas Bringas, Jacqueline Budrewicz, View ORCID ProfilePablo Lara-Gonzalez, View ORCID ProfileChristopher G. Sorensen-Turpin, View ORCID ProfileJoshua N. Bembenek, View ORCID ProfileDhanya K. Cheerambathur, View ORCID ProfileFederico Pelisch
doi: https://doi.org/10.1101/2020.06.12.148254
Laura Bel Borja
1Centre for Gene Regulation and Expression, Sir James Black Centre, School of Life Sciences, University of Dundee. Dundee, DD1 5EH, United Kingdom
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  • ORCID record for Laura Bel Borja
Flavie Soubigou
1Centre for Gene Regulation and Expression, Sir James Black Centre, School of Life Sciences, University of Dundee. Dundee, DD1 5EH, United Kingdom
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Samuel J.P. Taylor
1Centre for Gene Regulation and Expression, Sir James Black Centre, School of Life Sciences, University of Dundee. Dundee, DD1 5EH, United Kingdom
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Conchita Fraguas Bringas
1Centre for Gene Regulation and Expression, Sir James Black Centre, School of Life Sciences, University of Dundee. Dundee, DD1 5EH, United Kingdom
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Jacqueline Budrewicz
2Ludwig Institute for Cancer Research, San Diego, California, 92093, USA
3Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, 92093, USA
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Pablo Lara-Gonzalez
2Ludwig Institute for Cancer Research, San Diego, California, 92093, USA
3Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, 92093, USA
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Christopher G. Sorensen-Turpin
4Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN 37996, USA
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Joshua N. Bembenek
5Department of Molecular, Cellular, and Developmental Biology, University of Michigan. 1105 North University Ave., Ann Arbor, MI 48109-1085, USA
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Dhanya K. Cheerambathur
6Wellcome Centre for Cell Biology Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, EH9 3BF, UK
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  • ORCID record for Dhanya K. Cheerambathur
Federico Pelisch
1Centre for Gene Regulation and Expression, Sir James Black Centre, School of Life Sciences, University of Dundee. Dundee, DD1 5EH, United Kingdom
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  • For correspondence: f.pelisch@dundee.ac.uk
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Abstract

During cell division, a balance between protein kinases and phosphatases is required to achieve specific and highly regulated phosphorylation levels. Protein Phosphatase 2A (PP2A) is a heterotrimeric enzyme composed of Scaffold (A), Catalytic (C), and Regulatory (B) subunits. PP2A can be targeted to different locations by specific interactions with one of several possible B subunits. B56-type subunits play important roles during meiosis in yeast and mice, including the protection of centromeric cohesion (targeted by Shugoshin) and kinetochore-microtubule attachments (targeted by BubR1). Protection of sister chromatid cohesion during meiosis I in Caenorhabditis elegans (C. elegans) does not involve the classic Shugoshin-dependent pathway and the C. elegans BubR1 orthologue Mad3SAN-1 lacks the PP2A-recruiting domain. We exploited these features to address the role(s) and regulation of PP2A:B56 during C. elegans oocyte meiosis. We report here that PP2A:B56 is recruited to chromosomes and spindle and is essential for proper chromosome segregation during oocyte meiosis in C. elegans. Recruitment of PP2A:B56 is regulated temporally and spatially by the kinase BUB-1 and is dependent on a previously unrecognised LxxIxE short linear motif (SLiM) in BUB-1. Our results highlight a novel, BUB-1-dependent mechanism for PP2A:B56 recruitment, essential for proper chromosome segregation during meiosis I.

Competing Interest Statement

The authors have declared no competing interest.

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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 4.0 International license.
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PP2A:B56 Regulates Meiotic Chromosome Segregation in C. elegans Oocytes
Laura Bel Borja, Flavie Soubigou, Samuel J.P. Taylor, Conchita Fraguas Bringas, Jacqueline Budrewicz, Pablo Lara-Gonzalez, Christopher G. Sorensen-Turpin, Joshua N. Bembenek, Dhanya K. Cheerambathur, Federico Pelisch
bioRxiv 2020.06.12.148254; doi: https://doi.org/10.1101/2020.06.12.148254
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PP2A:B56 Regulates Meiotic Chromosome Segregation in C. elegans Oocytes
Laura Bel Borja, Flavie Soubigou, Samuel J.P. Taylor, Conchita Fraguas Bringas, Jacqueline Budrewicz, Pablo Lara-Gonzalez, Christopher G. Sorensen-Turpin, Joshua N. Bembenek, Dhanya K. Cheerambathur, Federico Pelisch
bioRxiv 2020.06.12.148254; doi: https://doi.org/10.1101/2020.06.12.148254

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