STIL is required for centriole duplication in human cells
Centrioles are key structural elements of centrosomes and primary cilia. In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication. STIL (SCL/TAL1 interrupting locus, also known as SIL) is a ce...
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Veröffentlicht in: | Journal of cell science 2012-03, Vol.125 (Pt 5), p.1353-1362 |
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creator | Vulprecht, Julia David, Ahuvit Tibelius, Alexandra Castiel, Asher Konotop, Gleb Liu, Fengying Bestvater, Felix Raab, Marc S Zentgraf, Hanswalter Izraeli, Shai Krämer, Alwin |
description | Centrioles are key structural elements of centrosomes and primary cilia. In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication. STIL (SCL/TAL1 interrupting locus, also known as SIL) is a centrosomal protein that is essential for mouse and zebrafish embryonic development and mutated in primary microcephaly. Here, we show that STIL localizes to the pericentriolar material surrounding parental centrioles. Its overexpression results in excess centriole formation. siRNA-mediated depletion of STIL leads to loss of centrioles and abrogates PLK4-induced centriole overduplication. Additionally, we show that STIL is necessary for SAS6 recruitment to centrioles, suggesting that it is essential for daughter centriole formation, interacts with the centromere protein CPAP and rapidly shuttles between the cytoplasm and centrioles. Consistent with the requirement of centrioles for cilia formation, Stil(-/-) mouse embryonic fibroblasts lack primary cilia--a phenotype that can be reverted by restoration of STIL expression. These findings demonstrate that STIL is an essential component of the centriole replication machinery in mammalian cells. |
doi_str_mv | 10.1242/jcs.104109 |
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In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication. STIL (SCL/TAL1 interrupting locus, also known as SIL) is a centrosomal protein that is essential for mouse and zebrafish embryonic development and mutated in primary microcephaly. Here, we show that STIL localizes to the pericentriolar material surrounding parental centrioles. Its overexpression results in excess centriole formation. siRNA-mediated depletion of STIL leads to loss of centrioles and abrogates PLK4-induced centriole overduplication. Additionally, we show that STIL is necessary for SAS6 recruitment to centrioles, suggesting that it is essential for daughter centriole formation, interacts with the centromere protein CPAP and rapidly shuttles between the cytoplasm and centrioles. Consistent with the requirement of centrioles for cilia formation, Stil(-/-) mouse embryonic fibroblasts lack primary cilia--a phenotype that can be reverted by restoration of STIL expression. These findings demonstrate that STIL is an essential component of the centriole replication machinery in mammalian cells.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.104109</identifier><identifier>PMID: 22349705</identifier><language>eng</language><publisher>England</publisher><subject>Cell Cycle ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Division - physiology ; Cell Line ; Centrioles - genetics ; Centrioles - metabolism ; Centrosome - physiology ; Cilia - metabolism ; Cytoplasm - physiology ; Danio rerio ; HEK293 Cells ; Humans ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Microtubule-Associated Proteins - metabolism ; Protein-Serine-Threonine Kinases - metabolism ; RNA Interference ; RNA, Small Interfering</subject><ispartof>Journal of cell science, 2012-03, Vol.125 (Pt 5), p.1353-1362</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-3eef974cc3bb136465cbecafffb874b009b5c627df84f2d558ab9e15788a9a483</citedby><cites>FETCH-LOGICAL-c421t-3eef974cc3bb136465cbecafffb874b009b5c627df84f2d558ab9e15788a9a483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3665,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22349705$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vulprecht, Julia</creatorcontrib><creatorcontrib>David, Ahuvit</creatorcontrib><creatorcontrib>Tibelius, Alexandra</creatorcontrib><creatorcontrib>Castiel, Asher</creatorcontrib><creatorcontrib>Konotop, Gleb</creatorcontrib><creatorcontrib>Liu, Fengying</creatorcontrib><creatorcontrib>Bestvater, Felix</creatorcontrib><creatorcontrib>Raab, Marc S</creatorcontrib><creatorcontrib>Zentgraf, Hanswalter</creatorcontrib><creatorcontrib>Izraeli, Shai</creatorcontrib><creatorcontrib>Krämer, Alwin</creatorcontrib><title>STIL is required for centriole duplication in human cells</title><title>Journal of cell science</title><addtitle>J Cell Sci</addtitle><description>Centrioles are key structural elements of centrosomes and primary cilia. In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication. STIL (SCL/TAL1 interrupting locus, also known as SIL) is a centrosomal protein that is essential for mouse and zebrafish embryonic development and mutated in primary microcephaly. Here, we show that STIL localizes to the pericentriolar material surrounding parental centrioles. Its overexpression results in excess centriole formation. siRNA-mediated depletion of STIL leads to loss of centrioles and abrogates PLK4-induced centriole overduplication. Additionally, we show that STIL is necessary for SAS6 recruitment to centrioles, suggesting that it is essential for daughter centriole formation, interacts with the centromere protein CPAP and rapidly shuttles between the cytoplasm and centrioles. Consistent with the requirement of centrioles for cilia formation, Stil(-/-) mouse embryonic fibroblasts lack primary cilia--a phenotype that can be reverted by restoration of STIL expression. These findings demonstrate that STIL is an essential component of the centriole replication machinery in mammalian cells.</description><subject>Cell Cycle</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Division - physiology</subject><subject>Cell Line</subject><subject>Centrioles - genetics</subject><subject>Centrioles - metabolism</subject><subject>Centrosome - physiology</subject><subject>Cilia - metabolism</subject><subject>Cytoplasm - physiology</subject><subject>Danio rerio</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90EtLAzEQwPEgiq3Vix9AclOErZPXZnOU4qNQ8GA9L0k2wZR9tMnuwW_fLa0ePc1hfgzDH6FbAnNCOX3a2DQnwAmoMzQlXMpMESbP0RSAkkwJxiboKqUNAEiq5CWaUMq4kiCmSH2ulyscEo5uN4ToKuy7iK1r-xi62uFq2NbB6j50LQ4t_h4a3Y7ruk7X6MLrOrmb05yhr9eX9eI9W328LRfPq8xySvqMOeeV5NYyYwjLeS6scVZ7700huQFQRticysoX3NNKiEIb5YiQRaGV5gWbofvj3W3sdoNLfdmEdPhAt64bUqkUUwSA0FE-_CsJ0AIozQUf6eOR2tilFJ0vtzE0Ov6MqDxELceo5THqiO9OdwfTuOqP_lZke7ctcS8</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>Vulprecht, Julia</creator><creator>David, Ahuvit</creator><creator>Tibelius, Alexandra</creator><creator>Castiel, Asher</creator><creator>Konotop, Gleb</creator><creator>Liu, Fengying</creator><creator>Bestvater, Felix</creator><creator>Raab, Marc S</creator><creator>Zentgraf, Hanswalter</creator><creator>Izraeli, Shai</creator><creator>Krämer, Alwin</creator><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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20120301</creationdate><title>STIL is required for centriole duplication in human cells</title><author>Vulprecht, Julia ; David, Ahuvit ; Tibelius, Alexandra ; Castiel, Asher ; Konotop, Gleb ; Liu, Fengying ; Bestvater, Felix ; Raab, Marc S ; Zentgraf, Hanswalter ; Izraeli, Shai ; Krämer, Alwin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-3eef974cc3bb136465cbecafffb874b009b5c627df84f2d558ab9e15788a9a483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Cell Cycle</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Division - physiology</topic><topic>Cell Line</topic><topic>Centrioles - genetics</topic><topic>Centrioles - metabolism</topic><topic>Centrosome - physiology</topic><topic>Cilia - metabolism</topic><topic>Cytoplasm - physiology</topic><topic>Danio rerio</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vulprecht, Julia</creatorcontrib><creatorcontrib>David, Ahuvit</creatorcontrib><creatorcontrib>Tibelius, Alexandra</creatorcontrib><creatorcontrib>Castiel, Asher</creatorcontrib><creatorcontrib>Konotop, Gleb</creatorcontrib><creatorcontrib>Liu, Fengying</creatorcontrib><creatorcontrib>Bestvater, Felix</creatorcontrib><creatorcontrib>Raab, Marc S</creatorcontrib><creatorcontrib>Zentgraf, Hanswalter</creatorcontrib><creatorcontrib>Izraeli, Shai</creatorcontrib><creatorcontrib>Krämer, Alwin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vulprecht, Julia</au><au>David, Ahuvit</au><au>Tibelius, Alexandra</au><au>Castiel, Asher</au><au>Konotop, Gleb</au><au>Liu, Fengying</au><au>Bestvater, Felix</au><au>Raab, Marc S</au><au>Zentgraf, Hanswalter</au><au>Izraeli, Shai</au><au>Krämer, Alwin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>STIL is required for centriole duplication in human cells</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2012-03-01</date><risdate>2012</risdate><volume>125</volume><issue>Pt 5</issue><spage>1353</spage><epage>1362</epage><pages>1353-1362</pages><issn>0021-9533</issn><eissn>1477-9137</eissn><abstract>Centrioles are key structural elements of centrosomes and primary cilia. In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication. STIL (SCL/TAL1 interrupting locus, also known as SIL) is a centrosomal protein that is essential for mouse and zebrafish embryonic development and mutated in primary microcephaly. Here, we show that STIL localizes to the pericentriolar material surrounding parental centrioles. Its overexpression results in excess centriole formation. siRNA-mediated depletion of STIL leads to loss of centrioles and abrogates PLK4-induced centriole overduplication. Additionally, we show that STIL is necessary for SAS6 recruitment to centrioles, suggesting that it is essential for daughter centriole formation, interacts with the centromere protein CPAP and rapidly shuttles between the cytoplasm and centrioles. Consistent with the requirement of centrioles for cilia formation, Stil(-/-) mouse embryonic fibroblasts lack primary cilia--a phenotype that can be reverted by restoration of STIL expression. These findings demonstrate that STIL is an essential component of the centriole replication machinery in mammalian cells.</abstract><cop>England</cop><pmid>22349705</pmid><doi>10.1242/jcs.104109</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Cell Cycle Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Division - physiology Cell Line Centrioles - genetics Centrioles - metabolism Centrosome - physiology Cilia - metabolism Cytoplasm - physiology Danio rerio HEK293 Cells Humans Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Microtubule-Associated Proteins - metabolism Protein-Serine-Threonine Kinases - metabolism RNA Interference RNA, Small Interfering |
title | STIL is required for centriole duplication in human cells |
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