Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B

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 bo...

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Detalles Bibliográficos
Autores: Novas, Rossina, Cardenas Rodríguez, Magdalena, Lepanto, Paola, Fabregat, Matías, Rodao, Magela, Fariello Rico, María Inés, Ramos, Mauricio, Davison, Camila, Casanova, Gabriela, Alfaja, L., Lecumberry, Federico, González Sapienza, Gualberto, Irigoín, Florencia, Badano, José L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:Uruguay
Institución:Universidad de la República
Repositorio:COLIBRI
Idioma:inglés
OAI Identifier:oai:colibri.udelar.edu.uy:20.500.12008/21997
Acceso en línea:https://hdl.handle.net/20.500.12008/21997
Access Level:acceso abierto
Palabra clave:Bardet-Biedl syndrome
Proteins
Phenotype
zebrafish
Descripción
Sumario: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.

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