The Kin1 kinase and the calcineurin phosphatase cooperate to link actin ring assembly and septum synthesis in fission yeast

Background information The Kin1 protein kinase of fission yeast, which regulates cell surface cohesiveness during interphase cell growth, is also present at the cell division site during mitosis; however, its function in cell division has remained elusive. Results In FK506‐mediated calcineurin defic...

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Veröffentlicht in:Biology of the cell 2013-03, Vol.105 (3), p.129-148
Hauptverfasser: Cadou, Angela, Couturier, Anne, Le Goff, Cathy, Xie, Linfeng, Paulson, James R., Le Goff, Xavier
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container_issue 3
container_start_page 129
container_title Biology of the cell
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creator Cadou, Angela
Couturier, Anne
Le Goff, Cathy
Xie, Linfeng
Paulson, James R.
Le Goff, Xavier
description Background information The Kin1 protein kinase of fission yeast, which regulates cell surface cohesiveness during interphase cell growth, is also present at the cell division site during mitosis; however, its function in cell division has remained elusive. Results In FK506‐mediated calcineurin deficient cells, mitosis is extended and ring formation is transiently compromised but septation remains normal. Here, we show that Kin1 inhibition in these cells leads to polyseptation and defects in membrane closure. Actomyosin ring disassembly is prevented and ultimately the daughter cells fail to separate. We show that the Pmk1 MAP kinase pathway and the type V myosin Myo4 act downstream of the cytokinetic function of Kin1. Kin1 inhibition also promotes polyseptation in myo3Δ, a type II myosin heavy‐chain mutant defective in ring assembly. In contrast, Kin1 inactivation rescues septation in a myosin light‐chain cdc4–8 thermosensitive mutant. A structure/function analysis of the Kin1 protein sequence identified a novel motif outside the kinase domain that is important for its polarised localisation and its catalytic activity. This motif is remarkably conserved in all fungal Kin1 homologues but is absent in related kinases of metazoans. Conclusions We conclude that calcineurin and Kin1 activities must be tightly coordinated to link actomyosin ring assembly with septum synthesis and membrane closure and to ensure separation of the daughter cells. In fission yeast, the function of the Kin1 protein kinase in cell division has remained elusive. In calcineurin phosphatase deficient cells, mitosis is extended and ring formation is transiently compromised but ultimately cell division is completed. Inhibition of Kin1 in these cells impinges on cytokinesis, preventing separation of the daughter cells. Thus, calcineurin and Kin1 activities must be tightly coordinated to link actin ring structure to septation at the end of the cell cycle in fission yeast.
doi_str_mv 10.1111/boc.201200042
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Results In FK506‐mediated calcineurin deficient cells, mitosis is extended and ring formation is transiently compromised but septation remains normal. Here, we show that Kin1 inhibition in these cells leads to polyseptation and defects in membrane closure. Actomyosin ring disassembly is prevented and ultimately the daughter cells fail to separate. We show that the Pmk1 MAP kinase pathway and the type V myosin Myo4 act downstream of the cytokinetic function of Kin1. Kin1 inhibition also promotes polyseptation in myo3Δ, a type II myosin heavy‐chain mutant defective in ring assembly. In contrast, Kin1 inactivation rescues septation in a myosin light‐chain cdc4–8 thermosensitive mutant. A structure/function analysis of the Kin1 protein sequence identified a novel motif outside the kinase domain that is important for its polarised localisation and its catalytic activity. This motif is remarkably conserved in all fungal Kin1 homologues but is absent in related kinases of metazoans. Conclusions We conclude that calcineurin and Kin1 activities must be tightly coordinated to link actomyosin ring assembly with septum synthesis and membrane closure and to ensure separation of the daughter cells. In fission yeast, the function of the Kin1 protein kinase in cell division has remained elusive. In calcineurin phosphatase deficient cells, mitosis is extended and ring formation is transiently compromised but ultimately cell division is completed. Inhibition of Kin1 in these cells impinges on cytokinesis, preventing separation of the daughter cells. 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Results In FK506‐mediated calcineurin deficient cells, mitosis is extended and ring formation is transiently compromised but septation remains normal. Here, we show that Kin1 inhibition in these cells leads to polyseptation and defects in membrane closure. Actomyosin ring disassembly is prevented and ultimately the daughter cells fail to separate. We show that the Pmk1 MAP kinase pathway and the type V myosin Myo4 act downstream of the cytokinetic function of Kin1. Kin1 inhibition also promotes polyseptation in myo3Δ, a type II myosin heavy‐chain mutant defective in ring assembly. In contrast, Kin1 inactivation rescues septation in a myosin light‐chain cdc4–8 thermosensitive mutant. A structure/function analysis of the Kin1 protein sequence identified a novel motif outside the kinase domain that is important for its polarised localisation and its catalytic activity. This motif is remarkably conserved in all fungal Kin1 homologues but is absent in related kinases of metazoans. Conclusions We conclude that calcineurin and Kin1 activities must be tightly coordinated to link actomyosin ring assembly with septum synthesis and membrane closure and to ensure separation of the daughter cells. In fission yeast, the function of the Kin1 protein kinase in cell division has remained elusive. In calcineurin phosphatase deficient cells, mitosis is extended and ring formation is transiently compromised but ultimately cell division is completed. Inhibition of Kin1 in these cells impinges on cytokinesis, preventing separation of the daughter cells. 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inhibitors</subject><subject>Protein-Serine-Threonine Kinases - chemistry</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyrimidines - pharmacology</subject><subject>Schizosaccharomyces - cytology</subject><subject>Schizosaccharomyces - drug effects</subject><subject>Schizosaccharomyces - enzymology</subject><subject>Schizosaccharomyces - growth &amp; development</subject><subject>Schizosaccharomyces pombe</subject><subject>Schizosaccharomyces pombe Proteins - antagonists &amp; inhibitors</subject><subject>Schizosaccharomyces pombe Proteins - chemistry</subject><subject>Schizosaccharomyces pombe Proteins - metabolism</subject><subject>Tacrolimus - pharmacology</subject><issn>0248-4900</issn><issn>1768-322X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0U2P0zAQBmALgdiycOSKfORAlvE4n8elgl2gYoVUBOJiOa5DTRM7m0mAiD-PS0vFCXyxZD9-NdbL2GMBFyKu53UwFwgCASDFO2whirxMJOKnu2wBmJZJWgGcsQdEX_ekKrP77AwlVqlEuWA_11vL3zov-M55TZZrv-FjPDO6Nc7baXCe99tA_VaP-3sTQm8HPVo-Bt46v-PajNFE94VrItvV7fw7hWw_Th2n2cc8csSjahyRC57PVtP4kN1rdEv20XE_Zx9evVwvr5PVzdXr5eUqMWlaYZKZTaNxYwAllAXqJs8yqIomL3MJjZVljbmFGrNapEaIDPPS6Bw3aPaflKk8Z88OuVvdqn5wnR5mFbRT15cr5TzZoVMAJVSI8puI_OmB90O4nSyNqnNkbNtqb8NESmQ5CFmIqvo_lSJOIEFApMmBmiEQDbY5TSJA7ZtUsUl1ajL6J8foqe7s5qT_VBdBcQDfXWvnf6epFzfLv6OPozga7Y_TSz3sVF7IIlMf313FkPRN8Vm8V2v5CxgNt5Q</recordid><startdate>201303</startdate><enddate>201303</enddate><creator>Cadou, Angela</creator><creator>Couturier, Anne</creator><creator>Le Goff, Cathy</creator><creator>Xie, Linfeng</creator><creator>Paulson, James R.</creator><creator>Le Goff, Xavier</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>M7N</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-5041-0468</orcidid></search><sort><creationdate>201303</creationdate><title>The Kin1 kinase and the calcineurin phosphatase cooperate to link actin ring assembly and septum synthesis in fission yeast</title><author>Cadou, Angela ; Couturier, Anne ; Le Goff, Cathy ; Xie, Linfeng ; Paulson, James R. ; Le Goff, Xavier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4492-5cdfa2dc0230872af655097f68630fe38b26e0b25b14c115268ca62d2c2943343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Actins - metabolism</topic><topic>Amino Acid Motifs</topic><topic>Amino Acid Sequence</topic><topic>Calcineurin</topic><topic>Cancer</topic><topic>Cell division</topic><topic>Cell Wall - drug effects</topic><topic>Cytokinesis</topic><topic>Cytokinesis - drug effects</topic><topic>Fungi</topic><topic>Genetics</topic><topic>Life Sciences</topic><topic>Metazoa</topic><topic>Molecular Sequence Data</topic><topic>Mutation - genetics</topic><topic>Myosin Heavy Chains - metabolism</topic><topic>Phenotype</topic><topic>Phosphoric Monoester Hydrolases - antagonists &amp; inhibitors</topic><topic>Phosphoric Monoester Hydrolases - metabolism</topic><topic>Protein serine/threonine kinase/phosphatase</topic><topic>Protein Transport - drug effects</topic><topic>Protein-Serine-Threonine Kinases - antagonists &amp; inhibitors</topic><topic>Protein-Serine-Threonine Kinases - chemistry</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyrimidines - pharmacology</topic><topic>Schizosaccharomyces - cytology</topic><topic>Schizosaccharomyces - drug effects</topic><topic>Schizosaccharomyces - enzymology</topic><topic>Schizosaccharomyces - growth &amp; development</topic><topic>Schizosaccharomyces pombe</topic><topic>Schizosaccharomyces pombe Proteins - antagonists &amp; inhibitors</topic><topic>Schizosaccharomyces pombe Proteins - chemistry</topic><topic>Schizosaccharomyces pombe Proteins - metabolism</topic><topic>Tacrolimus - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cadou, Angela</creatorcontrib><creatorcontrib>Couturier, Anne</creatorcontrib><creatorcontrib>Le Goff, Cathy</creatorcontrib><creatorcontrib>Xie, Linfeng</creatorcontrib><creatorcontrib>Paulson, James R.</creatorcontrib><creatorcontrib>Le Goff, Xavier</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Biology of the cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cadou, Angela</au><au>Couturier, Anne</au><au>Le Goff, Cathy</au><au>Xie, Linfeng</au><au>Paulson, James R.</au><au>Le Goff, Xavier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Kin1 kinase and the calcineurin phosphatase cooperate to link actin ring assembly and septum synthesis in fission yeast</atitle><jtitle>Biology of the cell</jtitle><addtitle>Biology of the Cell</addtitle><date>2013-03</date><risdate>2013</risdate><volume>105</volume><issue>3</issue><spage>129</spage><epage>148</epage><pages>129-148</pages><issn>0248-4900</issn><eissn>1768-322X</eissn><abstract>Background information The Kin1 protein kinase of fission yeast, which regulates cell surface cohesiveness during interphase cell growth, is also present at the cell division site during mitosis; however, its function in cell division has remained elusive. Results In FK506‐mediated calcineurin deficient cells, mitosis is extended and ring formation is transiently compromised but septation remains normal. Here, we show that Kin1 inhibition in these cells leads to polyseptation and defects in membrane closure. Actomyosin ring disassembly is prevented and ultimately the daughter cells fail to separate. We show that the Pmk1 MAP kinase pathway and the type V myosin Myo4 act downstream of the cytokinetic function of Kin1. Kin1 inhibition also promotes polyseptation in myo3Δ, a type II myosin heavy‐chain mutant defective in ring assembly. In contrast, Kin1 inactivation rescues septation in a myosin light‐chain cdc4–8 thermosensitive mutant. A structure/function analysis of the Kin1 protein sequence identified a novel motif outside the kinase domain that is important for its polarised localisation and its catalytic activity. This motif is remarkably conserved in all fungal Kin1 homologues but is absent in related kinases of metazoans. Conclusions We conclude that calcineurin and Kin1 activities must be tightly coordinated to link actomyosin ring assembly with septum synthesis and membrane closure and to ensure separation of the daughter cells. In fission yeast, the function of the Kin1 protein kinase in cell division has remained elusive. In calcineurin phosphatase deficient cells, mitosis is extended and ring formation is transiently compromised but ultimately cell division is completed. Inhibition of Kin1 in these cells impinges on cytokinesis, preventing separation of the daughter cells. Thus, calcineurin and Kin1 activities must be tightly coordinated to link actin ring structure to septation at the end of the cell cycle in fission yeast.</abstract><cop>Hoboken</cop><pub>WILEY-VCH Verlag</pub><pmid>23294323</pmid><doi>10.1111/boc.201200042</doi><tpages>20</tpages><orcidid>https://orcid.org/0000-0002-5041-0468</orcidid></addata></record>
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language eng
recordid cdi_hal_primary_oai_HAL_inserm_00809223v1
source MEDLINE; Access via Wiley Online Library
subjects Actins - metabolism
Amino Acid Motifs
Amino Acid Sequence
Calcineurin
Cancer
Cell division
Cell Wall - drug effects
Cytokinesis
Cytokinesis - drug effects
Fungi
Genetics
Life Sciences
Metazoa
Molecular Sequence Data
Mutation - genetics
Myosin Heavy Chains - metabolism
Phenotype
Phosphoric Monoester Hydrolases - antagonists & inhibitors
Phosphoric Monoester Hydrolases - metabolism
Protein serine/threonine kinase/phosphatase
Protein Transport - drug effects
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - chemistry
Protein-Serine-Threonine Kinases - metabolism
Pyrazoles - pharmacology
Pyrimidines - pharmacology
Schizosaccharomyces - cytology
Schizosaccharomyces - drug effects
Schizosaccharomyces - enzymology
Schizosaccharomyces - growth & development
Schizosaccharomyces pombe
Schizosaccharomyces pombe Proteins - antagonists & inhibitors
Schizosaccharomyces pombe Proteins - chemistry
Schizosaccharomyces pombe Proteins - metabolism
Tacrolimus - pharmacology
title The Kin1 kinase and the calcineurin phosphatase cooperate to link actin ring assembly and septum synthesis in fission yeast
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