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Defining how Pak1 regulates cell polarity and cell division in fission yeast

Joseph O. Magliozzi, Jack Sears, Marielle Brady, Hannah E. Opalko, Arminja N. Kettenbach, View ORCID ProfileJames B. Moseley
doi: https://doi.org/10.1101/722900
Joseph O. Magliozzi
1Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
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Jack Sears
1Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
2Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
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Marielle Brady
1Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
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Hannah E. Opalko
1Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
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Arminja N. Kettenbach
1Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
2Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
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James B. Moseley
1Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
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  • ORCID record for James B. Moseley
  • For correspondence: james.b.moseley@dartmouth.edu
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ABSTRACT

Protein kinases direct polarized growth by regulating the cytoskeleton in time and space, and could play similar roles in cell division. We found that the Cdc42-activated polarity kinase Pak1 colocalizes with the assembling cytokinetic ring and remains at the division site during septation. Mutations in pak1 led to defects in cytokinetic ring assembly and cell separation. Through a phosphoproteomic screen, we identified novel Pak1 targets that function in polarized growth, cytokinesis, and septation. For cytokinesis, we found that Pak1 regulates the localization of its substrates Mid1 and Cdc15 to the cytokinetic ring. For cell separation, Pak1 phosphorylates the RNA-binding protein Sts5 to prevent its assembly into granules. These results show that Pak1 acts directly on components of the cytokinetic ring, and unexpectedly promotes the later stages of cell division by inhibiting the assembly of ribonucleoprotein granules. More broadly, our work reveals that cell polarity signaling proteins coordinate diverse events to promote cell division at the end of the cell cycle.

SUMMARY Magliozzi et al. show that fission yeast Pak1 regulates multiple events during cell division. Through a phosphoproteomic screen and subsequent mutant analysis, their work uncovers direct targets and mechanisms for Pak1 activity during cell growth and division.

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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-ND 4.0 International license.
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Posted August 02, 2019.
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Defining how Pak1 regulates cell polarity and cell division in fission yeast
Joseph O. Magliozzi, Jack Sears, Marielle Brady, Hannah E. Opalko, Arminja N. Kettenbach, James B. Moseley
bioRxiv 722900; doi: https://doi.org/10.1101/722900
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Defining how Pak1 regulates cell polarity and cell division in fission yeast
Joseph O. Magliozzi, Jack Sears, Marielle Brady, Hannah E. Opalko, Arminja N. Kettenbach, James B. Moseley
bioRxiv 722900; doi: https://doi.org/10.1101/722900

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