The NanceHoran syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology
Identifieur interne : 001223 ( Istex/Corpus ); précédent : 001222; suivant : 001224The NanceHoran syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology
Auteurs : Simon P. Brooks ; Margherita Coccia ; Hao R. Tang ; Naheed Kanuga ; Laura M. Machesky ; Maryse Bailly ; Michael E. Cheetham ; Alison J. HardcastleSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2010-06-15.
Abstract
NanceHoran syndrome (NHS) is an X-linked developmental disorder, characterized by bilateral congenital cataracts, dental anomalies, facial dysmorphism and mental retardation. Null mutations in a novel gene, NHS, cause the syndrome. The NHS gene appears to have multiple isoforms as a result of alternative transcription, but a cellular function for the NHS protein has yet to be defined. We describe NHS as a founder member of a new protein family (NHS, NHSL1 and NHSL2). Here, we demonstrate that NHS is a novel regulator of actin remodelling and cell morphology. NHS localizes to sites of cellcell contact, the leading edge of lamellipodia and focal adhesions. The N-terminus of isoforms NHS-A and NHS-1A, implicated in the pathogenesis of NHS, have a functional WAVE homology domain that interacts with the Abi protein family, haematopoietic stem/progenitor cell protein 300 (HSPC300), Nap1 and Sra1. NHS knockdown resulted in the disruption of the actin cytoskeleton. We show that NHS controls cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. NHS knockdown led to a striking increase in cell spreading. Conversely, ectopic overexpression of NHS inhibited lamellipod formation. Remodelling of the actin cytoskeleton and localized actin polymerization into branched actin filaments at the plasma membrane are essential for mediating changes in cell shape, migration and cell contact. Our data identify NHS as a new regulator of actin remodelling. We suggest that NHS orchestrates actin regulatory protein function in response to signalling events during development.
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DOI: 10.1093/hmg/ddq125
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Hardcastle</name><affiliation><mods:affiliation>UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK and</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: a.hardcastle@ucl.ac.uk</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2010-06-15">2010-06-15</date><biblScope unit="volume">19</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="2421">2421</biblScope><biblScope unit="page" to="2432">2432</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">0288EE5210B924F537652F32E015566CC0815CE2</idno><idno type="DOI">10.1093/hmg/ddq125</idno><idno type="ArticleID">ddq125</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">NanceHoran syndrome (NHS) is an X-linked developmental disorder, characterized by bilateral congenital cataracts, dental anomalies, facial dysmorphism and mental retardation. Null mutations in a novel gene, NHS, cause the syndrome. The NHS gene appears to have multiple isoforms as a result of alternative transcription, but a cellular function for the NHS protein has yet to be defined. We describe NHS as a founder member of a new protein family (NHS, NHSL1 and NHSL2). Here, we demonstrate that NHS is a novel regulator of actin remodelling and cell morphology. NHS localizes to sites of cellcell contact, the leading edge of lamellipodia and focal adhesions. The N-terminus of isoforms NHS-A and NHS-1A, implicated in the pathogenesis of NHS, have a functional WAVE homology domain that interacts with the Abi protein family, haematopoietic stem/progenitor cell protein 300 (HSPC300), Nap1 and Sra1. NHS knockdown resulted in the disruption of the actin cytoskeleton. We show that NHS controls cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. NHS knockdown led to a striking increase in cell spreading. Conversely, ectopic overexpression of NHS inhibited lamellipod formation. Remodelling of the actin cytoskeleton and localized actin polymerization into branched actin filaments at the plasma membrane are essential for mediating changes in cell shape, migration and cell contact. Our data identify NHS as a new regulator of actin remodelling. We suggest that NHS orchestrates actin regulatory protein function in response to signalling events during development.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Simon P. Brooks</name><affiliations><json:string>UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK and</json:string></affiliations></json:item><json:item><name>Margherita Coccia</name><affiliations><json:string>UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK and</json:string></affiliations></json:item><json:item><name>Hao R. 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NHS localizes to sites of cellcell contact, the leading edge of lamellipodia and focal adhesions. The N-terminus of isoforms NHS-A and NHS-1A, implicated in the pathogenesis of NHS, have a functional WAVE homology domain that interacts with the Abi protein family, haematopoietic stem/progenitor cell protein 300 (HSPC300), Nap1 and Sra1. NHS knockdown resulted in the disruption of the actin cytoskeleton. We show that NHS controls cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. NHS knockdown led to a striking increase in cell spreading. Conversely, ectopic overexpression of NHS inhibited lamellipod formation. Remodelling of the actin cytoskeleton and localized actin polymerization into branched actin filaments at the plasma membrane are essential for mediating changes in cell shape, migration and cell contact. Our data identify NHS as a new regulator of actin remodelling. 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Null mutations in a novel gene, NHS, cause the syndrome. The NHS gene appears to have multiple isoforms as a result of alternative transcription, but a cellular function for the NHS protein has yet to be defined. We describe NHS as a founder member of a new protein family (NHS, NHSL1 and NHSL2). Here, we demonstrate that NHS is a novel regulator of actin remodelling and cell morphology. NHS localizes to sites of cellcell contact, the leading edge of lamellipodia and focal adhesions. The N-terminus of isoforms NHS-A and NHS-1A, implicated in the pathogenesis of NHS, have a functional WAVE homology domain that interacts with the Abi protein family, haematopoietic stem/progenitor cell protein 300 (HSPC300), Nap1 and Sra1. NHS knockdown resulted in the disruption of the actin cytoskeleton. We show that NHS controls cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. NHS knockdown led to a striking increase in cell spreading. Conversely, ectopic overexpression of NHS inhibited lamellipod formation. Remodelling of the actin cytoskeleton and localized actin polymerization into branched actin filaments at the plasma membrane are essential for mediating changes in cell shape, migration and cell contact. Our data identify NHS as a new regulator of actin remodelling. We suggest that NHS orchestrates actin regulatory protein function in response to signalling events during development.</p></abstract></profileDesc><revisionDesc><change when="2010-03-23">Created</change><change when="2010-06-15">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-10-14">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/0288EE5210B924F537652F32E015566CC0815CE2/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-id journal-id-type="hwp">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/hmg/ddq125</article-id><article-id pub-id-type="publisher-id">ddq125</article-id><article-categories><subj-group subj-group-type="heading"><subject>ARTICLES</subject></subj-group></article-categories><title-group><article-title>The Nance–Horan syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Brooks</surname><given-names>Simon P.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Coccia</surname><given-names>Margherita</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Tang</surname><given-names>Hao R.</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kanuga</surname><given-names>Naheed</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Machesky</surname><given-names>Laura M.</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bailly</surname><given-names>Maryse</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cheetham</surname><given-names>Michael E.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hardcastle</surname><given-names>Alison J.</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="af1"><label>1</label><institution>UCL Institute of Ophthalmology</institution>, <addr-line>11-43 Bath Street, London EC1V 9EL</addr-line>, <country>UK</country> and</aff><aff id="af2"><label>2</label><institution>The CRUK Beatson Institute for Cancer Research</institution>, <addr-line>Glasgow G61 1BD</addr-line>, <country>UK</country></aff><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed. Tel: <phone>+44 2076086945</phone>; Fax: <fax>+44 2076084002</fax>; Email: <email>a.hardcastle@ucl.ac.uk</email></corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>6</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>23</day><month>3</month><year>2010</year></pub-date><volume>19</volume><issue>12</issue><fpage>2421</fpage><lpage>2432</lpage><history><date date-type="received"><day>19</day><month>2</month><year>2010</year></date><date date-type="accepted"><day>20</day><month>3</month><year>2010</year></date></history><permissions><copyright-statement>© The Author 2010. Published by Oxford University Press</copyright-statement><copyright-year>2010</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/uk/"><p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</p></license></permissions><abstract><p>Nance–Horan syndrome (NHS) is an X-linked developmental disorder, characterized by bilateral congenital cataracts, dental anomalies, facial dysmorphism and mental retardation. Null mutations in a novel gene, <italic>NHS</italic>, cause the syndrome. The <italic>NHS</italic> gene appears to have multiple isoforms as a result of alternative transcription, but a cellular function for the NHS protein has yet to be defined. We describe NHS as a founder member of a new protein family (NHS, NHSL1 and NHSL2). Here, we demonstrate that NHS is a novel regulator of actin remodelling and cell morphology. NHS localizes to sites of cell–cell contact, the leading edge of lamellipodia and focal adhesions. The N-terminus of isoforms NHS-A and NHS-1A, implicated in the pathogenesis of NHS, have a functional WAVE homology domain that interacts with the Abi protein family, haematopoietic stem/progenitor cell protein 300 (HSPC300), Nap1 and Sra1. NHS knockdown resulted in the disruption of the actin cytoskeleton. We show that NHS controls cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. NHS knockdown led to a striking increase in cell spreading. Conversely, ectopic overexpression of NHS inhibited lamellipod formation. Remodelling of the actin cytoskeleton and localized actin polymerization into branched actin filaments at the plasma membrane are essential for mediating changes in cell shape, migration and cell contact. Our data identify NHS as a new regulator of actin remodelling. We suggest that NHS orchestrates actin regulatory protein function in response to signalling events during development.</p></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>The NanceHoran syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>The NanceHoran syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology</title></titleInfo><name type="personal"><namePart type="given">Simon P.</namePart><namePart type="family">Brooks</namePart><affiliation>UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Margherita</namePart><namePart type="family">Coccia</namePart><affiliation>UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hao R.</namePart><namePart type="family">Tang</namePart><affiliation>The CRUK Beatson Institute for Cancer Research, Glasgow G61 1BD, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Naheed</namePart><namePart type="family">Kanuga</namePart><affiliation>UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Laura M.</namePart><namePart type="family">Machesky</namePart><affiliation>The CRUK Beatson Institute for Cancer Research, Glasgow G61 1BD, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maryse</namePart><namePart type="family">Bailly</namePart><affiliation>UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael E.</namePart><namePart type="family">Cheetham</namePart><affiliation>UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alison J.</namePart><namePart type="family">Hardcastle</namePart><affiliation>UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK and</affiliation><affiliation>E-mail: a.hardcastle@ucl.ac.uk</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2010-06-15</dateIssued><dateCreated encoding="w3cdtf">2010-03-23</dateCreated><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>NanceHoran syndrome (NHS) is an X-linked developmental disorder, characterized by bilateral congenital cataracts, dental anomalies, facial dysmorphism and mental retardation. Null mutations in a novel gene, NHS, cause the syndrome. The NHS gene appears to have multiple isoforms as a result of alternative transcription, but a cellular function for the NHS protein has yet to be defined. We describe NHS as a founder member of a new protein family (NHS, NHSL1 and NHSL2). Here, we demonstrate that NHS is a novel regulator of actin remodelling and cell morphology. NHS localizes to sites of cellcell contact, the leading edge of lamellipodia and focal adhesions. The N-terminus of isoforms NHS-A and NHS-1A, implicated in the pathogenesis of NHS, have a functional WAVE homology domain that interacts with the Abi protein family, haematopoietic stem/progenitor cell protein 300 (HSPC300), Nap1 and Sra1. NHS knockdown resulted in the disruption of the actin cytoskeleton. We show that NHS controls cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. NHS knockdown led to a striking increase in cell spreading. Conversely, ectopic overexpression of NHS inhibited lamellipod formation. Remodelling of the actin cytoskeleton and localized actin polymerization into branched actin filaments at the plasma membrane are essential for mediating changes in cell shape, migration and cell contact. Our data identify NHS as a new regulator of actin remodelling. We suggest that NHS orchestrates actin regulatory protein function in response to signalling events during development.</abstract><relatedItem type="host"><titleInfo><title>Human Molecular Genetics</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0964-6906</identifier><identifier type="eISSN">1460-2083</identifier><identifier type="PublisherID">hmg</identifier><identifier type="PublisherID-hwp">hmg</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>19</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>2421</start><end>2432</end></extent></part></relatedItem><identifier type="istex">0288EE5210B924F537652F32E015566CC0815CE2</identifier><identifier type="DOI">10.1093/hmg/ddq125</identifier><identifier type="ArticleID">ddq125</identifier><accessCondition type="use and reproduction" contentType="copyright">The Author 2010. 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