xbx-4, a homolog of the Joubert syndrome gene FAM149B1, acts via the CCRK and RCK kinase cascade to regulate cilia morphology.
Curr Biol
; 31(24): 5642-5649.e5, 2021 12 20.
Article
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| MEDLINE
| ID: mdl-34731674
ABSTRACT
Primary cilia are microtubule (MT)-based organelles that mediate sensory functions in multiple cell types. Disruption of cilia structure or function leads to a diverse collection of diseases termed ciliopathies.1-3 The highly conserved CCRK and RCK kinases (ICK/MOK/MAK) negatively regulate cilia length and structure in Chlamydomonas, C. elegans, and mammalian cells.4-10 How the activity of this kinase cascade is tuned to precisely regulate cilia architecture is unclear. Mutations in the Domain of Unknown Function 3719 (DUF3719)-containing protein FAM149B1 have recently been shown to elongate cilia via unknown mechanisms and result in the ciliopathy Joubert syndrome.11 Here we identify XBX-4, a DUF3719-containing protein related to human FAM149B1, as a regulator of the DYF-18 CCRK and DYF-5 MAK kinase pathway in C. elegans. As in dyf-18 and dyf-5 mutants,10 sensory neuron cilia are elongated in xbx-4 mutants and exhibit stabilized axonemal MTs. XBX-4 promotes DYF-18 CCRK function to regulate localization and function of DYF-5 MAK. We find that Joubert syndrome-associated mutations in the XBX-4 DUF3719 domain also elongate cilia in C. elegans. Our results identify a new metazoan-specific regulator of this highly conserved kinase pathway and suggest that FAM149B1 may similarly act via the CCRK/RCK kinase pathway to regulate ciliary homeostasis in humans.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cilios
/
Proteínas de Caenorhabditis elegans
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Biol
Asunto de la revista:
BIOLOGIA
Año:
2021
Tipo del documento:
Article