A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened
Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein tr...
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| Veröffentlicht in: | PLoS genetics 2011-11, Vol.7 (11), p.e1002358-e1002358 |
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| creator | Seo, Seongjin Zhang, Qihong Bugge, Kevin Breslow, David K Searby, Charles C Nachury, Maxence V Sheffield, Val C |
| description | Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling. |
| doi_str_mv | 10.1371/journal.pgen.1002358 |
| format | Article |
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Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1002358</identifier><identifier>PMID: 22072986</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Bardet-Biedl syndrome ; Bardet-Biedl Syndrome - genetics ; Bardet-Biedl Syndrome - metabolism ; Bars ; Biology ; Cells ; Cilia - genetics ; Cilia - metabolism ; Cytomegalovirus ; Experiments ; Genetic disorders ; Hedgehog Proteins - metabolism ; HEK293 Cells ; Humans ; Kidney diseases ; Mass spectrometry ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - metabolism ; Physiological aspects ; Protein Transport - genetics ; Proteins ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Rodents ; Signal Transduction ; Smoothened Receptor ; Studies ; Transcription factors ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>PLoS genetics, 2011-11, Vol.7 (11), p.e1002358-e1002358</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>Seo et al. 2011</rights><rights>2011 Seo et al. 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: Seo S, Zhang Q, Bugge K, Breslow DK, Searby CC, et al. (2011) A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened. 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Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling.</description><subject>Animals</subject><subject>Bardet-Biedl syndrome</subject><subject>Bardet-Biedl Syndrome - genetics</subject><subject>Bardet-Biedl Syndrome - metabolism</subject><subject>Bars</subject><subject>Biology</subject><subject>Cells</subject><subject>Cilia - genetics</subject><subject>Cilia - metabolism</subject><subject>Cytomegalovirus</subject><subject>Experiments</subject><subject>Genetic disorders</subject><subject>Hedgehog Proteins - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Kidney diseases</subject><subject>Mass spectrometry</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Physiological aspects</subject><subject>Protein Transport - genetics</subject><subject>Proteins</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Smoothened Receptor</subject><subject>Studies</subject><subject>Transcription factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVksGO0zAQhiMEYpeFN0AQCQnEocWO7cS5IHVXLFSqWEEXDlwsJ5mkLo5dbGcFb49Ls6tG4gDywdb4m9-efyZJnmI0x6TAb7Z2cEbq-a4DM8cIZYTxe8kpZozMCoro_aPzSfLI-y1CESmLh8lJlqEiK3l-mnxapMbegE53zgZQJl19u75c4dRBN2gZwKe10kq6X2lwsm1V_V2ZLrVtGjaQnp-vbQ-pNE267q2NIQPN4-RBK7WHJ-N-lny5fHd98WG2unq_vFisZnVO8zCTDDFEaV00RYZzhOKB1qTCHBhlss0aViJcEU6hIBXLyopnqCkzhHOGSl4ycpY8P-jutPVidMMLTDCJCnmeRWJ5IBort2LnVB_rEFYq8SdgXSekC6rWIAoOnHCOK8oqijHmTRUVeMsaSaAtSdR6O742VD00NZjoh56ITm-M2ojO3ggSrS4xigKvRgFnfwzgg-iVr0FracAOXpSI5DlmPI_kiwPZyfgzZVobBes9LRZZEVvPKN2XP_8LFVcDvaqtgVbF-CTh9SQhMgF-hk4O3ovl-vN_sB__nb36OmVfHrEbkDpsvNVDUNb4KUgPYO2s9w7aO6cxEvvxv2242I-_GMc_pj077tJd0u28k99n1fwE</recordid><startdate>20111101</startdate><enddate>20111101</enddate><creator>Seo, Seongjin</creator><creator>Zhang, Qihong</creator><creator>Bugge, Kevin</creator><creator>Breslow, David K</creator><creator>Searby, Charles C</creator><creator>Nachury, Maxence V</creator><creator>Sheffield, Val C</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></search><sort><creationdate>20111101</creationdate><title>A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened</title><author>Seo, Seongjin ; Zhang, Qihong ; Bugge, Kevin ; Breslow, David K ; Searby, Charles C ; Nachury, Maxence V ; Sheffield, Val C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c646t-a505044c7d721600c7d4c3b18e545af2d5901b384e73b529b820d920165098953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Bardet-Biedl syndrome</topic><topic>Bardet-Biedl Syndrome - genetics</topic><topic>Bardet-Biedl Syndrome - metabolism</topic><topic>Bars</topic><topic>Biology</topic><topic>Cells</topic><topic>Cilia - genetics</topic><topic>Cilia - metabolism</topic><topic>Cytomegalovirus</topic><topic>Experiments</topic><topic>Genetic disorders</topic><topic>Hedgehog Proteins - metabolism</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Kidney diseases</topic><topic>Mass spectrometry</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Physiological aspects</topic><topic>Protein Transport - genetics</topic><topic>Proteins</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Smoothened Receptor</topic><topic>Studies</topic><topic>Transcription factors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seo, Seongjin</creatorcontrib><creatorcontrib>Zhang, Qihong</creatorcontrib><creatorcontrib>Bugge, Kevin</creatorcontrib><creatorcontrib>Breslow, David K</creatorcontrib><creatorcontrib>Searby, Charles C</creatorcontrib><creatorcontrib>Nachury, Maxence V</creatorcontrib><creatorcontrib>Sheffield, Val C</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><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seo, Seongjin</au><au>Zhang, Qihong</au><au>Bugge, Kevin</au><au>Breslow, David K</au><au>Searby, Charles C</au><au>Nachury, Maxence V</au><au>Sheffield, Val C</au><au>Barsh, Gregory S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2011-11-01</date><risdate>2011</risdate><volume>7</volume><issue>11</issue><spage>e1002358</spage><epage>e1002358</epage><pages>e1002358-e1002358</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22072986</pmid><doi>10.1371/journal.pgen.1002358</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bardet-Biedl syndrome Bardet-Biedl Syndrome - genetics Bardet-Biedl Syndrome - metabolism Bars Biology Cells Cilia - genetics Cilia - metabolism Cytomegalovirus Experiments Genetic disorders Hedgehog Proteins - metabolism HEK293 Cells Humans Kidney diseases Mass spectrometry Mice Mice, Inbred C57BL Mice, Transgenic Microtubule-Associated Proteins - genetics Microtubule-Associated Proteins - metabolism Physiological aspects Protein Transport - genetics Proteins Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - metabolism RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Rodents Signal Transduction Smoothened Receptor Studies Transcription factors Transcription Factors - genetics Transcription Factors - metabolism |
| title | A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened |
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