Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B
| Autor: | Federico Lecumberry, Lucía Alfaya, Camila Davison, Gabriela Casanova, Jose L. Badano, Paola Lepanto, Florencia Irigoín, Rossina Novas, Mauricio Ramos, María Inés Fariello, Magela Rodao, Matías Fabregat, Gualberto González-Sapienza, Magdalena Cardenas-Rodriguez |
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| Přispěvatelé: | Novas, Rosina. Instituto Pasteur (Montevideo), Cardenas Rodríguez, Magdalena. Instituto Pasteur (Montevideo), Lepanto, Paola. Instituto Pasteur (Montevideo), Fabregat, Matías. Instituto Pasteur (Montevideo), Rodao, Magela. Universidad de la República (Uruguay). Facultad de Ciencias. Unidad de Microscopía, Fariello, María Inés. Instituto Pasteur (Montevideo), Ramos, Mauricio. Instituto Pasteur (Montevideo), Davison, Camilia. Universidad de la República (Uruguay). Facultad de Ciencias. Unidad de Microscopía, Casanova, Gabriela. Universidad de la República (Uruguay). Facultad de Ciencias. Unidad de Microscopía, Lecumberry, Federico. Instituto Pasteur (Montevideo), Irigoín, Florencia. Instituto Pasteur (Montevideo), Badano, José L. Instituto Pasteur (Montevideo) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Science Nuclear Localization Signals Kinesins Cell Cycle Proteins Article 03 medical and health sciences 0302 clinical medicine Bardet–Biedl syndrome Ciliogenesis Bardet-Biedl syndrome medicine Animals Humans Clustered Regularly Interspaced Short Palindromic Repeats Cilia Obesity education Bardet-Biedl Syndrome Zebrafish education.field_of_study Multidisciplinary biology Cilium Retinal Degeneration Proteins Morphant Zebrafish Proteins zebrafish medicine.disease biology.organism_classification Cell biology Cytoskeletal Proteins Polydactyly Protein Transport Ciliopathy Phenotype HEK293 Cells 030104 developmental biology Kinesin light chain 1 Mutation Kinesin Medicine 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-16 (2018) Scientific Reports COLIBRI Universidad de la República instacron:Universidad de la República |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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