The PP2A/4/6 subfamily of phosphoprotein phosphatases regulates DAF-16 and confers resistance to environmental stress in postreproductive adult C. elegans
Insulin and insulin-like growth factors are longevity determinants that negatively regulate Forkhead box class O (FoxO) transcription factors. In C. elegans mutations that constitutively activate DAF-16, the ortholog of mammalian FoxO3a, extend lifespan by two-fold. While environmental insults induc...
Gespeichert in:
| Veröffentlicht in: | PloS one 2020-12, Vol.15 (12), p.e0229812-e0229812 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0229812 |
|---|---|
| container_issue | 12 |
| container_start_page | e0229812 |
| container_title | PloS one |
| container_volume | 15 |
| creator | Rivard, Rebecca S Morris, Julia M Youngman, Matthew J |
| description | Insulin and insulin-like growth factors are longevity determinants that negatively regulate Forkhead box class O (FoxO) transcription factors. In C. elegans mutations that constitutively activate DAF-16, the ortholog of mammalian FoxO3a, extend lifespan by two-fold. While environmental insults induce DAF-16 activity in younger animals, it also becomes activated in an age-dependent manner in the absence of stress, modulating gene expression well into late adulthood. The mechanism by which DAF-16 activity is regulated during aging has not been defined. Since phosphorylation of DAF-16 generally leads to its inhibition, we asked whether phosphatases might be necessary for its increased transcriptional activity in adult C. elegans. We focused on the PP2A/4/6 subfamily of phosphoprotein phosphatases, members of which had been implicated to regulate DAF-16 under low insulin signaling conditions but had not been investigated during aging in wildtype animals. Using reverse genetics, we functionally characterized all C. elegans orthologs of human catalytic, regulatory, and scaffolding subunits of PP2A/4/6 holoenzymes in postreproductive adults. We found that PP2A complex constituents PAA-1 and PPTR-1 regulate DAF-16 transcriptional activity during aging and that they cooperate with the catalytic subunit LET-92 to protect adult animals from ultraviolet radiation. PP4 complex members PPH-4.1/4.2, and SMK-1 also appear to regulate DAF-16 in an age-dependent manner, and together with PPFR-2 they contribute to innate immunity. Interestingly, SUR-6 but no other subunit of the PP2A complex was necessary for the survival of pathogen-infected animals. Finally, we found that PP6 complex constituents PPH-6 and SAPS-1 contribute to host defense during aging, apparently without affecting DAF-16 transcriptional activity. Our studies indicate that a set of PP2A/4/6 complexes protect adult C. elegans from environmental stress, thus preserving healthspan. Therefore, along with their functions in cell division and development, the PP2A/4/6 phosphatases also appear to play critical roles later in life. |
| doi_str_mv | 10.1371/journal.pone.0229812 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2470010339</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A645383171</galeid><doaj_id>oai_doaj_org_article_d65e567c3d2d4d799e5a441a8197bd5d</doaj_id><sourcerecordid>A645383171</sourcerecordid><originalsourceid>FETCH-LOGICAL-c641t-7dac55762e4158364eb926477fc25aca55386fd96705bf0353762da453e915ae3</originalsourceid><addsrcrecordid>eNqNk1FrFDEQxxdRbK1-A9GAIPpw181mk9y-CEe1Wii0aPU1zG1m71JyyZlkD_tV_LRmvW3pSR9kCTvJ_OafzAxTFC9pOaVM0uNr3wcHdrrxDqdlVTUzWj0qDmnDqomoSvb4nn1QPIvxuiw5mwnxtDhgjFE-k-Vh8ftqheTyspof18eCxH7RwdrYG-I7sln5mNcm-ITGjVtIEDGSgMveQsrWx_nphAoCTpPWuw7D4IwmJnAtkuQJuq0J3q3RJbAkpuyNZNDzg53Vdd8ms0UCureJnEwJWlyCi8-LJx3YiC_G_1Hx_fTT1cmXyfnF57OT-fmkFTVNE6mh5VyKCuucExM1LppK1FJ2bcWhBT4k3elGyJIvupJxllkNNWfYUA7IjorXO92N9VGNZY2qqmVZ0pKxJhNnO0J7uFabYNYQbpQHo_4e-LBUEJJpLSotOHIhW6YrXWvZNMihrinMaCMXmuus9WG8rV-sUbe5LAHsnui-x5mVWvqtkpJxkTt4VLwbBYL_2WNMam1ii9aCQ9_v3l3NWFXXGX3zD_pwdiO1hJyAcZ3P97aDqJqLXKYZo5JmavoAlT-Na5M7j53J53sB7_cCMpPwV1pCH6M6-_b1_9mLH_vs23vsCsGmVfS2T8a7uA_WO7ANPsaA3V2RaamGEbqthhpGSI0jlMNe3W_QXdDtzLA_d-cXGQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2470010339</pqid></control><display><type>article</type><title>The PP2A/4/6 subfamily of phosphoprotein phosphatases regulates DAF-16 and confers resistance to environmental stress in postreproductive adult C. elegans</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Rivard, Rebecca S ; Morris, Julia M ; Youngman, Matthew J</creator><contributor>Massiah, Michael</contributor><creatorcontrib>Rivard, Rebecca S ; Morris, Julia M ; Youngman, Matthew J ; Massiah, Michael</creatorcontrib><description>Insulin and insulin-like growth factors are longevity determinants that negatively regulate Forkhead box class O (FoxO) transcription factors. In C. elegans mutations that constitutively activate DAF-16, the ortholog of mammalian FoxO3a, extend lifespan by two-fold. While environmental insults induce DAF-16 activity in younger animals, it also becomes activated in an age-dependent manner in the absence of stress, modulating gene expression well into late adulthood. The mechanism by which DAF-16 activity is regulated during aging has not been defined. Since phosphorylation of DAF-16 generally leads to its inhibition, we asked whether phosphatases might be necessary for its increased transcriptional activity in adult C. elegans. We focused on the PP2A/4/6 subfamily of phosphoprotein phosphatases, members of which had been implicated to regulate DAF-16 under low insulin signaling conditions but had not been investigated during aging in wildtype animals. Using reverse genetics, we functionally characterized all C. elegans orthologs of human catalytic, regulatory, and scaffolding subunits of PP2A/4/6 holoenzymes in postreproductive adults. We found that PP2A complex constituents PAA-1 and PPTR-1 regulate DAF-16 transcriptional activity during aging and that they cooperate with the catalytic subunit LET-92 to protect adult animals from ultraviolet radiation. PP4 complex members PPH-4.1/4.2, and SMK-1 also appear to regulate DAF-16 in an age-dependent manner, and together with PPFR-2 they contribute to innate immunity. Interestingly, SUR-6 but no other subunit of the PP2A complex was necessary for the survival of pathogen-infected animals. Finally, we found that PP6 complex constituents PPH-6 and SAPS-1 contribute to host defense during aging, apparently without affecting DAF-16 transcriptional activity. Our studies indicate that a set of PP2A/4/6 complexes protect adult C. elegans from environmental stress, thus preserving healthspan. Therefore, along with their functions in cell division and development, the PP2A/4/6 phosphatases also appear to play critical roles later in life.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0229812</identifier><identifier>PMID: 33315870</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adults ; Age ; Aging ; Aging - metabolism ; Animals ; Bacterial infections ; Biology ; Biology and life sciences ; Caenorhabditis elegans ; Caenorhabditis elegans - genetics ; Caenorhabditis elegans - metabolism ; Caenorhabditis elegans Proteins - metabolism ; Caenorhabditis elegans Proteins - physiology ; Cell cycle ; Cell division ; Constituents ; Environmental stress ; Enzymes ; Forkhead protein ; Forkhead Transcription Factors - metabolism ; Forkhead Transcription Factors - physiology ; FOXO3 protein ; Gene expression ; Genetic aspects ; Genetics ; Growth factors ; Infections ; Innate immunity ; Insulin ; Insulin-like growth factors ; Kinases ; Life span ; Ligands ; Longevity - genetics ; Medicine and Health Sciences ; Mutation ; People and Places ; Phosphatase ; Phosphatases ; Phosphoprotein Phosphatases - metabolism ; Phosphorylation ; Physical Sciences ; Physiological aspects ; Protein Phosphatase 2 - metabolism ; Protein Phosphatase 2 - physiology ; Proteins ; Research and Analysis Methods ; Scaffolding ; Signal Transduction ; Stress (Physiology) ; Stress, Physiological - physiology ; Transcription factors ; Ultraviolet radiation ; Worms</subject><ispartof>PloS one, 2020-12, Vol.15 (12), p.e0229812-e0229812</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Rivard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Rivard et al 2020 Rivard et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c641t-7dac55762e4158364eb926477fc25aca55386fd96705bf0353762da453e915ae3</cites><orcidid>0000-0002-9889-3323</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735605/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735605/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33315870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Massiah, Michael</contributor><creatorcontrib>Rivard, Rebecca S</creatorcontrib><creatorcontrib>Morris, Julia M</creatorcontrib><creatorcontrib>Youngman, Matthew J</creatorcontrib><title>The PP2A/4/6 subfamily of phosphoprotein phosphatases regulates DAF-16 and confers resistance to environmental stress in postreproductive adult C. elegans</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Insulin and insulin-like growth factors are longevity determinants that negatively regulate Forkhead box class O (FoxO) transcription factors. In C. elegans mutations that constitutively activate DAF-16, the ortholog of mammalian FoxO3a, extend lifespan by two-fold. While environmental insults induce DAF-16 activity in younger animals, it also becomes activated in an age-dependent manner in the absence of stress, modulating gene expression well into late adulthood. The mechanism by which DAF-16 activity is regulated during aging has not been defined. Since phosphorylation of DAF-16 generally leads to its inhibition, we asked whether phosphatases might be necessary for its increased transcriptional activity in adult C. elegans. We focused on the PP2A/4/6 subfamily of phosphoprotein phosphatases, members of which had been implicated to regulate DAF-16 under low insulin signaling conditions but had not been investigated during aging in wildtype animals. Using reverse genetics, we functionally characterized all C. elegans orthologs of human catalytic, regulatory, and scaffolding subunits of PP2A/4/6 holoenzymes in postreproductive adults. We found that PP2A complex constituents PAA-1 and PPTR-1 regulate DAF-16 transcriptional activity during aging and that they cooperate with the catalytic subunit LET-92 to protect adult animals from ultraviolet radiation. PP4 complex members PPH-4.1/4.2, and SMK-1 also appear to regulate DAF-16 in an age-dependent manner, and together with PPFR-2 they contribute to innate immunity. Interestingly, SUR-6 but no other subunit of the PP2A complex was necessary for the survival of pathogen-infected animals. Finally, we found that PP6 complex constituents PPH-6 and SAPS-1 contribute to host defense during aging, apparently without affecting DAF-16 transcriptional activity. Our studies indicate that a set of PP2A/4/6 complexes protect adult C. elegans from environmental stress, thus preserving healthspan. Therefore, along with their functions in cell division and development, the PP2A/4/6 phosphatases also appear to play critical roles later in life.</description><subject>Adults</subject><subject>Age</subject><subject>Aging</subject><subject>Aging - metabolism</subject><subject>Animals</subject><subject>Bacterial infections</subject><subject>Biology</subject><subject>Biology and life sciences</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - genetics</subject><subject>Caenorhabditis elegans - metabolism</subject><subject>Caenorhabditis elegans Proteins - metabolism</subject><subject>Caenorhabditis elegans Proteins - physiology</subject><subject>Cell cycle</subject><subject>Cell division</subject><subject>Constituents</subject><subject>Environmental stress</subject><subject>Enzymes</subject><subject>Forkhead protein</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Forkhead Transcription Factors - physiology</subject><subject>FOXO3 protein</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Growth factors</subject><subject>Infections</subject><subject>Innate immunity</subject><subject>Insulin</subject><subject>Insulin-like growth factors</subject><subject>Kinases</subject><subject>Life span</subject><subject>Ligands</subject><subject>Longevity - genetics</subject><subject>Medicine and Health Sciences</subject><subject>Mutation</subject><subject>People and Places</subject><subject>Phosphatase</subject><subject>Phosphatases</subject><subject>Phosphoprotein Phosphatases - metabolism</subject><subject>Phosphorylation</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Protein Phosphatase 2 - metabolism</subject><subject>Protein Phosphatase 2 - physiology</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Scaffolding</subject><subject>Signal Transduction</subject><subject>Stress (Physiology)</subject><subject>Stress, Physiological - physiology</subject><subject>Transcription factors</subject><subject>Ultraviolet radiation</subject><subject>Worms</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1FrFDEQxxdRbK1-A9GAIPpw181mk9y-CEe1Wii0aPU1zG1m71JyyZlkD_tV_LRmvW3pSR9kCTvJ_OafzAxTFC9pOaVM0uNr3wcHdrrxDqdlVTUzWj0qDmnDqomoSvb4nn1QPIvxuiw5mwnxtDhgjFE-k-Vh8ftqheTyspof18eCxH7RwdrYG-I7sln5mNcm-ITGjVtIEDGSgMveQsrWx_nphAoCTpPWuw7D4IwmJnAtkuQJuq0J3q3RJbAkpuyNZNDzg53Vdd8ms0UCureJnEwJWlyCi8-LJx3YiC_G_1Hx_fTT1cmXyfnF57OT-fmkFTVNE6mh5VyKCuucExM1LppK1FJ2bcWhBT4k3elGyJIvupJxllkNNWfYUA7IjorXO92N9VGNZY2qqmVZ0pKxJhNnO0J7uFabYNYQbpQHo_4e-LBUEJJpLSotOHIhW6YrXWvZNMihrinMaCMXmuus9WG8rV-sUbe5LAHsnui-x5mVWvqtkpJxkTt4VLwbBYL_2WNMam1ii9aCQ9_v3l3NWFXXGX3zD_pwdiO1hJyAcZ3P97aDqJqLXKYZo5JmavoAlT-Na5M7j53J53sB7_cCMpPwV1pCH6M6-_b1_9mLH_vs23vsCsGmVfS2T8a7uA_WO7ANPsaA3V2RaamGEbqthhpGSI0jlMNe3W_QXdDtzLA_d-cXGQ</recordid><startdate>20201214</startdate><enddate>20201214</enddate><creator>Rivard, Rebecca S</creator><creator>Morris, Julia M</creator><creator>Youngman, Matthew J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9889-3323</orcidid></search><sort><creationdate>20201214</creationdate><title>The PP2A/4/6 subfamily of phosphoprotein phosphatases regulates DAF-16 and confers resistance to environmental stress in postreproductive adult C. elegans</title><author>Rivard, Rebecca S ; Morris, Julia M ; Youngman, Matthew J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c641t-7dac55762e4158364eb926477fc25aca55386fd96705bf0353762da453e915ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adults</topic><topic>Age</topic><topic>Aging</topic><topic>Aging - metabolism</topic><topic>Animals</topic><topic>Bacterial infections</topic><topic>Biology</topic><topic>Biology and life sciences</topic><topic>Caenorhabditis elegans</topic><topic>Caenorhabditis elegans - genetics</topic><topic>Caenorhabditis elegans - metabolism</topic><topic>Caenorhabditis elegans Proteins - metabolism</topic><topic>Caenorhabditis elegans Proteins - physiology</topic><topic>Cell cycle</topic><topic>Cell division</topic><topic>Constituents</topic><topic>Environmental stress</topic><topic>Enzymes</topic><topic>Forkhead protein</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Forkhead Transcription Factors - physiology</topic><topic>FOXO3 protein</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Genetics</topic><topic>Growth factors</topic><topic>Infections</topic><topic>Innate immunity</topic><topic>Insulin</topic><topic>Insulin-like growth factors</topic><topic>Kinases</topic><topic>Life span</topic><topic>Ligands</topic><topic>Longevity - genetics</topic><topic>Medicine and Health Sciences</topic><topic>Mutation</topic><topic>People and Places</topic><topic>Phosphatase</topic><topic>Phosphatases</topic><topic>Phosphoprotein Phosphatases - metabolism</topic><topic>Phosphorylation</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Protein Phosphatase 2 - metabolism</topic><topic>Protein Phosphatase 2 - physiology</topic><topic>Proteins</topic><topic>Research and Analysis Methods</topic><topic>Scaffolding</topic><topic>Signal Transduction</topic><topic>Stress (Physiology)</topic><topic>Stress, Physiological - physiology</topic><topic>Transcription factors</topic><topic>Ultraviolet radiation</topic><topic>Worms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rivard, Rebecca S</creatorcontrib><creatorcontrib>Morris, Julia M</creatorcontrib><creatorcontrib>Youngman, Matthew J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rivard, Rebecca S</au><au>Morris, Julia M</au><au>Youngman, Matthew J</au><au>Massiah, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The PP2A/4/6 subfamily of phosphoprotein phosphatases regulates DAF-16 and confers resistance to environmental stress in postreproductive adult C. elegans</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-12-14</date><risdate>2020</risdate><volume>15</volume><issue>12</issue><spage>e0229812</spage><epage>e0229812</epage><pages>e0229812-e0229812</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Insulin and insulin-like growth factors are longevity determinants that negatively regulate Forkhead box class O (FoxO) transcription factors. In C. elegans mutations that constitutively activate DAF-16, the ortholog of mammalian FoxO3a, extend lifespan by two-fold. While environmental insults induce DAF-16 activity in younger animals, it also becomes activated in an age-dependent manner in the absence of stress, modulating gene expression well into late adulthood. The mechanism by which DAF-16 activity is regulated during aging has not been defined. Since phosphorylation of DAF-16 generally leads to its inhibition, we asked whether phosphatases might be necessary for its increased transcriptional activity in adult C. elegans. We focused on the PP2A/4/6 subfamily of phosphoprotein phosphatases, members of which had been implicated to regulate DAF-16 under low insulin signaling conditions but had not been investigated during aging in wildtype animals. Using reverse genetics, we functionally characterized all C. elegans orthologs of human catalytic, regulatory, and scaffolding subunits of PP2A/4/6 holoenzymes in postreproductive adults. We found that PP2A complex constituents PAA-1 and PPTR-1 regulate DAF-16 transcriptional activity during aging and that they cooperate with the catalytic subunit LET-92 to protect adult animals from ultraviolet radiation. PP4 complex members PPH-4.1/4.2, and SMK-1 also appear to regulate DAF-16 in an age-dependent manner, and together with PPFR-2 they contribute to innate immunity. Interestingly, SUR-6 but no other subunit of the PP2A complex was necessary for the survival of pathogen-infected animals. Finally, we found that PP6 complex constituents PPH-6 and SAPS-1 contribute to host defense during aging, apparently without affecting DAF-16 transcriptional activity. Our studies indicate that a set of PP2A/4/6 complexes protect adult C. elegans from environmental stress, thus preserving healthspan. Therefore, along with their functions in cell division and development, the PP2A/4/6 phosphatases also appear to play critical roles later in life.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33315870</pmid><doi>10.1371/journal.pone.0229812</doi><tpages>e0229812</tpages><orcidid>https://orcid.org/0000-0002-9889-3323</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-12, Vol.15 (12), p.e0229812-e0229812 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2470010339 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adults Age Aging Aging - metabolism Animals Bacterial infections Biology Biology and life sciences Caenorhabditis elegans Caenorhabditis elegans - genetics Caenorhabditis elegans - metabolism Caenorhabditis elegans Proteins - metabolism Caenorhabditis elegans Proteins - physiology Cell cycle Cell division Constituents Environmental stress Enzymes Forkhead protein Forkhead Transcription Factors - metabolism Forkhead Transcription Factors - physiology FOXO3 protein Gene expression Genetic aspects Genetics Growth factors Infections Innate immunity Insulin Insulin-like growth factors Kinases Life span Ligands Longevity - genetics Medicine and Health Sciences Mutation People and Places Phosphatase Phosphatases Phosphoprotein Phosphatases - metabolism Phosphorylation Physical Sciences Physiological aspects Protein Phosphatase 2 - metabolism Protein Phosphatase 2 - physiology Proteins Research and Analysis Methods Scaffolding Signal Transduction Stress (Physiology) Stress, Physiological - physiology Transcription factors Ultraviolet radiation Worms |
| title | The PP2A/4/6 subfamily of phosphoprotein phosphatases regulates DAF-16 and confers resistance to environmental stress in postreproductive adult C. elegans |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T14%3A38%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20PP2A/4/6%20subfamily%20of%20phosphoprotein%20phosphatases%20regulates%20DAF-16%20and%20confers%20resistance%20to%20environmental%20stress%20in%20postreproductive%20adult%20C.%20elegans&rft.jtitle=PloS%20one&rft.au=Rivard,%20Rebecca%20S&rft.date=2020-12-14&rft.volume=15&rft.issue=12&rft.spage=e0229812&rft.epage=e0229812&rft.pages=e0229812-e0229812&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0229812&rft_dat=%3Cgale_plos_%3EA645383171%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2470010339&rft_id=info:pmid/33315870&rft_galeid=A645383171&rft_doaj_id=oai_doaj_org_article_d65e567c3d2d4d799e5a441a8197bd5d&rfr_iscdi=true |