The polarity protein Scribble regulates myelination and remyelination in the central nervous system
The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribbl...
Gespeichert in:
| Veröffentlicht in: | PLoS biology 2015-03, Vol.13 (3), p.e1002107-e1002107 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e1002107 |
|---|---|
| container_issue | 3 |
| container_start_page | e1002107 |
| container_title | PLoS biology |
| container_volume | 13 |
| creator | Jarjour, Andrew A Boyd, Amanda Dow, Lukas E Holloway, Rebecca K Goebbels, Sandra Humbert, Patrick O Williams, Anna ffrench-Constant, Charles |
| description | The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribble in CNS myelination and remyelination. Scribble is expressed throughout oligodendroglial development and is up-regulated in mature oligodendrocytes where it is localised to both developing and mature CNS myelin sheaths. Knockdown of Scribble expression in cultured oligodendroglia results in disrupted morphology and myelination initiation. When Scribble expression is conditionally eliminated in the myelinating glia of transgenic mice, myelin initiation in CNS is disrupted, both during development and following focal demyelination, and longitudinal extension of the myelin sheath is disrupted. At later stages of myelination, Scribble acts to negatively regulate myelin thickness whilst suppressing the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAP) kinase pathway, and localises to non-compact myelin flanking the node of Ranvier where it is required for paranodal axo-glial adhesion. These findings demonstrate an essential role for the evolutionarily-conserved regulators of intracellular polarity in myelination and remyelination. |
| doi_str_mv | 10.1371/journal.pbio.1002107 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1685022883</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A418846190</galeid><doaj_id>oai_doaj_org_article_66807c3dc1214268828929b4e77180c2</doaj_id><sourcerecordid>A418846190</sourcerecordid><originalsourceid>FETCH-LOGICAL-c667t-a9d8d147fc0aa6bff56bd66321bfc162b41a8feb1ab4386e2db9f891be19d5553</originalsourceid><addsrcrecordid>eNqVkktv3CAUha2qVfNo_0HVWuomXczUYAx4UymK-hgpaqQm7RYBvp4wwjABHHX-fZmME81IXbTyAuvyncPlcIviDarmqGbo48qPwUk7Xyvj56iqMKrYs-IYNaSZMc6b53v_R8VJjKvM4Bbzl8URbnjFKoqPC31zC-XaWxlM2pTr4BMYV17rYJSyUAZYjlYmiOWwAWucTMa7Urou7-xXsiZlIw0uBWlLB-Hej7GMm5hgeFW86KWN8HpaT4ufXz7fXHybXV59XVycX840pSzNZNvxDhHW60pKqvq-oaqjtMZI9RpRrAiSvAeFpCI1p4A71fa8RQpQ2zVNU58W73a-a-ujmPKJAlHe5JtzXmdisSM6L1diHcwgw0Z4acRDwYelkCEZbUFQmiPSdacRRgRTzjFvcasIMIZ4pXH2-jSdNqoBuunqB6aHO87ciqW_F6RmdfvQ7tlkEPzdCDGJwUQN1koHObzcN2U14Yhtz3q_Q5cyt2Zc77Oj3uLinCDOCUVtlan5X6j8dTAY7R30JtcPBB8OBJlJ8Dst5RijWFz_-A_2-7-zV78OWbJjdfAxBuifEkSV2A7640OK7aCLadCz7O1--k-ix8mu_wAvnvos</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1667348172</pqid></control><display><type>article</type><title>The polarity protein Scribble regulates myelination and remyelination in the central nervous system</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Jarjour, Andrew A ; Boyd, Amanda ; Dow, Lukas E ; Holloway, Rebecca K ; Goebbels, Sandra ; Humbert, Patrick O ; Williams, Anna ; ffrench-Constant, Charles</creator><creatorcontrib>Jarjour, Andrew A ; Boyd, Amanda ; Dow, Lukas E ; Holloway, Rebecca K ; Goebbels, Sandra ; Humbert, Patrick O ; Williams, Anna ; ffrench-Constant, Charles</creatorcontrib><description>The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribble in CNS myelination and remyelination. Scribble is expressed throughout oligodendroglial development and is up-regulated in mature oligodendrocytes where it is localised to both developing and mature CNS myelin sheaths. Knockdown of Scribble expression in cultured oligodendroglia results in disrupted morphology and myelination initiation. When Scribble expression is conditionally eliminated in the myelinating glia of transgenic mice, myelin initiation in CNS is disrupted, both during development and following focal demyelination, and longitudinal extension of the myelin sheath is disrupted. At later stages of myelination, Scribble acts to negatively regulate myelin thickness whilst suppressing the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAP) kinase pathway, and localises to non-compact myelin flanking the node of Ranvier where it is required for paranodal axo-glial adhesion. These findings demonstrate an essential role for the evolutionarily-conserved regulators of intracellular polarity in myelination and remyelination.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.1002107</identifier><identifier>PMID: 25807062</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Cell Polarity ; Central nervous system ; Central Nervous System - metabolism ; Central Nervous System - ultrastructure ; Extracellular Signal-Regulated MAP Kinases - genetics ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Gene Expression Regulation ; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Kinases ; Mice ; Mice, Transgenic ; Multiple sclerosis ; Nervous system ; Neuropeptides ; Oligodendroglia - metabolism ; Oligodendroglia - ultrastructure ; Phosphatase ; Physiological aspects ; Proteins ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Rodents ; Signal Transduction</subject><ispartof>PLoS biology, 2015-03, Vol.13 (3), p.e1002107-e1002107</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Jarjour et al 2015 Jarjour et al</rights><rights>2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Jarjour AA, Boyd A, Dow LE, Holloway RK, Goebbels S, Humbert PO, et al. (2015) The Polarity Protein Scribble Regulates Myelination and Remyelination in the Central Nervous System. PLoS Biol 13(3): e1002107. doi:10.1371/journal.pbio.1002107</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c667t-a9d8d147fc0aa6bff56bd66321bfc162b41a8feb1ab4386e2db9f891be19d5553</citedby><cites>FETCH-LOGICAL-c667t-a9d8d147fc0aa6bff56bd66321bfc162b41a8feb1ab4386e2db9f891be19d5553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373955/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373955/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25807062$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jarjour, Andrew A</creatorcontrib><creatorcontrib>Boyd, Amanda</creatorcontrib><creatorcontrib>Dow, Lukas E</creatorcontrib><creatorcontrib>Holloway, Rebecca K</creatorcontrib><creatorcontrib>Goebbels, Sandra</creatorcontrib><creatorcontrib>Humbert, Patrick O</creatorcontrib><creatorcontrib>Williams, Anna</creatorcontrib><creatorcontrib>ffrench-Constant, Charles</creatorcontrib><title>The polarity protein Scribble regulates myelination and remyelination in the central nervous system</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribble in CNS myelination and remyelination. Scribble is expressed throughout oligodendroglial development and is up-regulated in mature oligodendrocytes where it is localised to both developing and mature CNS myelin sheaths. Knockdown of Scribble expression in cultured oligodendroglia results in disrupted morphology and myelination initiation. When Scribble expression is conditionally eliminated in the myelinating glia of transgenic mice, myelin initiation in CNS is disrupted, both during development and following focal demyelination, and longitudinal extension of the myelin sheath is disrupted. At later stages of myelination, Scribble acts to negatively regulate myelin thickness whilst suppressing the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAP) kinase pathway, and localises to non-compact myelin flanking the node of Ranvier where it is required for paranodal axo-glial adhesion. These findings demonstrate an essential role for the evolutionarily-conserved regulators of intracellular polarity in myelination and remyelination.</description><subject>Animals</subject><subject>Cell Polarity</subject><subject>Central nervous system</subject><subject>Central Nervous System - metabolism</subject><subject>Central Nervous System - ultrastructure</subject><subject>Extracellular Signal-Regulated MAP Kinases - genetics</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Kinases</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Multiple sclerosis</subject><subject>Nervous system</subject><subject>Neuropeptides</subject><subject>Oligodendroglia - metabolism</subject><subject>Oligodendroglia - ultrastructure</subject><subject>Phosphatase</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><issn>1545-7885</issn><issn>1544-9173</issn><issn>1545-7885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVkktv3CAUha2qVfNo_0HVWuomXczUYAx4UymK-hgpaqQm7RYBvp4wwjABHHX-fZmME81IXbTyAuvyncPlcIviDarmqGbo48qPwUk7Xyvj56iqMKrYs-IYNaSZMc6b53v_R8VJjKvM4Bbzl8URbnjFKoqPC31zC-XaWxlM2pTr4BMYV17rYJSyUAZYjlYmiOWwAWucTMa7Urou7-xXsiZlIw0uBWlLB-Hej7GMm5hgeFW86KWN8HpaT4ufXz7fXHybXV59XVycX840pSzNZNvxDhHW60pKqvq-oaqjtMZI9RpRrAiSvAeFpCI1p4A71fa8RQpQ2zVNU58W73a-a-ujmPKJAlHe5JtzXmdisSM6L1diHcwgw0Z4acRDwYelkCEZbUFQmiPSdacRRgRTzjFvcasIMIZ4pXH2-jSdNqoBuunqB6aHO87ciqW_F6RmdfvQ7tlkEPzdCDGJwUQN1koHObzcN2U14Yhtz3q_Q5cyt2Zc77Oj3uLinCDOCUVtlan5X6j8dTAY7R30JtcPBB8OBJlJ8Dst5RijWFz_-A_2-7-zV78OWbJjdfAxBuifEkSV2A7640OK7aCLadCz7O1--k-ix8mu_wAvnvos</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Jarjour, Andrew A</creator><creator>Boyd, Amanda</creator><creator>Dow, Lukas E</creator><creator>Holloway, Rebecca K</creator><creator>Goebbels, Sandra</creator><creator>Humbert, Patrick O</creator><creator>Williams, Anna</creator><creator>ffrench-Constant, Charles</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>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><scope>CZG</scope></search><sort><creationdate>20150301</creationdate><title>The polarity protein Scribble regulates myelination and remyelination in the central nervous system</title><author>Jarjour, Andrew A ; Boyd, Amanda ; Dow, Lukas E ; Holloway, Rebecca K ; Goebbels, Sandra ; Humbert, Patrick O ; Williams, Anna ; ffrench-Constant, Charles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c667t-a9d8d147fc0aa6bff56bd66321bfc162b41a8feb1ab4386e2db9f891be19d5553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Cell Polarity</topic><topic>Central nervous system</topic><topic>Central Nervous System - metabolism</topic><topic>Central Nervous System - ultrastructure</topic><topic>Extracellular Signal-Regulated MAP Kinases - genetics</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Kinases</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Multiple sclerosis</topic><topic>Nervous system</topic><topic>Neuropeptides</topic><topic>Oligodendroglia - metabolism</topic><topic>Oligodendroglia - ultrastructure</topic><topic>Phosphatase</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jarjour, Andrew A</creatorcontrib><creatorcontrib>Boyd, Amanda</creatorcontrib><creatorcontrib>Dow, Lukas E</creatorcontrib><creatorcontrib>Holloway, Rebecca K</creatorcontrib><creatorcontrib>Goebbels, Sandra</creatorcontrib><creatorcontrib>Humbert, Patrick O</creatorcontrib><creatorcontrib>Williams, Anna</creatorcontrib><creatorcontrib>ffrench-Constant, Charles</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: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jarjour, Andrew A</au><au>Boyd, Amanda</au><au>Dow, Lukas E</au><au>Holloway, Rebecca K</au><au>Goebbels, Sandra</au><au>Humbert, Patrick O</au><au>Williams, Anna</au><au>ffrench-Constant, Charles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The polarity protein Scribble regulates myelination and remyelination in the central nervous system</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>13</volume><issue>3</issue><spage>e1002107</spage><epage>e1002107</epage><pages>e1002107-e1002107</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribble in CNS myelination and remyelination. Scribble is expressed throughout oligodendroglial development and is up-regulated in mature oligodendrocytes where it is localised to both developing and mature CNS myelin sheaths. Knockdown of Scribble expression in cultured oligodendroglia results in disrupted morphology and myelination initiation. When Scribble expression is conditionally eliminated in the myelinating glia of transgenic mice, myelin initiation in CNS is disrupted, both during development and following focal demyelination, and longitudinal extension of the myelin sheath is disrupted. At later stages of myelination, Scribble acts to negatively regulate myelin thickness whilst suppressing the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAP) kinase pathway, and localises to non-compact myelin flanking the node of Ranvier where it is required for paranodal axo-glial adhesion. These findings demonstrate an essential role for the evolutionarily-conserved regulators of intracellular polarity in myelination and remyelination.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25807062</pmid><doi>10.1371/journal.pbio.1002107</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1545-7885 |
| ispartof | PLoS biology, 2015-03, Vol.13 (3), p.e1002107-e1002107 |
| issn | 1545-7885 1544-9173 1545-7885 |
| language | eng |
| recordid | cdi_plos_journals_1685022883 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Cell Polarity Central nervous system Central Nervous System - metabolism Central Nervous System - ultrastructure Extracellular Signal-Regulated MAP Kinases - genetics Extracellular Signal-Regulated MAP Kinases - metabolism Gene Expression Regulation Intracellular Signaling Peptides and Proteins - antagonists & inhibitors Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Kinases Mice Mice, Transgenic Multiple sclerosis Nervous system Neuropeptides Oligodendroglia - metabolism Oligodendroglia - ultrastructure Phosphatase Physiological aspects Proteins RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Rodents Signal Transduction |
| title | The polarity protein Scribble regulates myelination and remyelination in the central nervous system |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T12%3A34%3A58IST&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%20polarity%20protein%20Scribble%20regulates%20myelination%20and%20remyelination%20in%20the%20central%20nervous%20system&rft.jtitle=PLoS%20biology&rft.au=Jarjour,%20Andrew%20A&rft.date=2015-03-01&rft.volume=13&rft.issue=3&rft.spage=e1002107&rft.epage=e1002107&rft.pages=e1002107-e1002107&rft.issn=1545-7885&rft.eissn=1545-7885&rft_id=info:doi/10.1371/journal.pbio.1002107&rft_dat=%3Cgale_plos_%3EA418846190%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=1667348172&rft_id=info:pmid/25807062&rft_galeid=A418846190&rft_doaj_id=oai_doaj_org_article_66807c3dc1214268828929b4e77180c2&rfr_iscdi=true |