Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B
Abstract Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal disease and mental retardation. CCDC28B is a BBS-associated protein that we have previously shown plays a role in cilia length regulation whereby its depletion results in shortened...
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Nature Portfolio
2018
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oai:doaj.org-article:b12b6dca1e794eb5831efb3cd85642352021-12-02T15:07:55ZKinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B10.1038/s41598-018-21329-62045-2322https://doaj.org/article/b12b6dca1e794eb5831efb3cd85642352018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21329-6https://doaj.org/toc/2045-2322Abstract Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal disease and mental retardation. CCDC28B is a BBS-associated protein that we have previously shown plays a role in cilia length regulation whereby its depletion results in shortened cilia both in cells and Danio rerio (zebrafish). At least part of that role is achieved by its interaction with the mTORC2 component SIN1, but the mechanistic details of this interaction and/or additional functions that CCDC28B might play in the context of cilia remain poorly understood. Here we uncover a novel interaction between CCDC28B and the kinesin 1 molecular motor that is relevant to cilia. CCDC28B interacts with kinesin light chain 1 (KLC1) and the heavy chain KIF5B. Notably, depletion of these kinesin 1 components results in abnormally elongated cilia. Furthermore, through genetic interaction studies we demonstrate that kinesin 1 regulates ciliogenesis through CCDC28B. We show that kinesin 1 regulates the subcellular distribution of CCDC28B, unexpectedly, inhibiting its nuclear accumulation, and a ccdc28b mutant missing a nuclear localization motif fails to rescue the phenotype in zebrafish morphant embryos. Therefore, we uncover a previously unknown role of kinesin 1 in cilia length regulation that relies on the BBS related protein CCDC28B.Rossina NovasMagdalena Cardenas-RodriguezPaola LepantoMatías FabregatMagela RodaoMaría Inés FarielloMauricio RamosCamila DavisonGabriela CasanovaLucía AlfayaFederico LecumberryGualberto González-SapienzaFlorencia IrigoínJose L. BadanoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-16 (2018) |
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Medicine R Science Q Rossina Novas Magdalena Cardenas-Rodriguez Paola Lepanto Matías Fabregat Magela Rodao María Inés Fariello Mauricio Ramos Camila Davison Gabriela Casanova Lucía Alfaya Federico Lecumberry Gualberto González-Sapienza Florencia Irigoín Jose L. Badano Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B |
| description |
Abstract Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal disease and mental retardation. CCDC28B is a BBS-associated protein that we have previously shown plays a role in cilia length regulation whereby its depletion results in shortened cilia both in cells and Danio rerio (zebrafish). At least part of that role is achieved by its interaction with the mTORC2 component SIN1, but the mechanistic details of this interaction and/or additional functions that CCDC28B might play in the context of cilia remain poorly understood. Here we uncover a novel interaction between CCDC28B and the kinesin 1 molecular motor that is relevant to cilia. CCDC28B interacts with kinesin light chain 1 (KLC1) and the heavy chain KIF5B. Notably, depletion of these kinesin 1 components results in abnormally elongated cilia. Furthermore, through genetic interaction studies we demonstrate that kinesin 1 regulates ciliogenesis through CCDC28B. We show that kinesin 1 regulates the subcellular distribution of CCDC28B, unexpectedly, inhibiting its nuclear accumulation, and a ccdc28b mutant missing a nuclear localization motif fails to rescue the phenotype in zebrafish morphant embryos. Therefore, we uncover a previously unknown role of kinesin 1 in cilia length regulation that relies on the BBS related protein CCDC28B. |
| format |
article |
| author |
Rossina Novas Magdalena Cardenas-Rodriguez Paola Lepanto Matías Fabregat Magela Rodao María Inés Fariello Mauricio Ramos Camila Davison Gabriela Casanova Lucía Alfaya Federico Lecumberry Gualberto González-Sapienza Florencia Irigoín Jose L. Badano |
| author_facet |
Rossina Novas Magdalena Cardenas-Rodriguez Paola Lepanto Matías Fabregat Magela Rodao María Inés Fariello Mauricio Ramos Camila Davison Gabriela Casanova Lucía Alfaya Federico Lecumberry Gualberto González-Sapienza Florencia Irigoín Jose L. Badano |
| author_sort |
Rossina Novas |
| title |
Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B |
| title_short |
Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B |
| title_full |
Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B |
| title_fullStr |
Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B |
| title_full_unstemmed |
Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B |
| title_sort |
kinesin 1 regulates cilia length through an interaction with the bardet-biedl syndrome related protein ccdc28b |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/b12b6dca1e794eb5831efb3cd8564235 |
| work_keys_str_mv |
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1718388341192261632 |