Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F20%3A00536280" target="_blank" >RIV/67985904:_____/20:00536280 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/20:00114425 RIV/00159816:_____/20:00073506 RIV/00027162:_____/20:N0000214
Result on the web
<a href="https://www.embopress.org/doi/full/10.15252/emmm.201911739" target="_blank" >https://www.embopress.org/doi/full/10.15252/emmm.201911739</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.15252/emmm.201911739" target="_blank" >10.15252/emmm.201911739</a>

Result language
angličtina
Original language name
Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling
Original language description
Mutations in genes affecting primary cilia cause ciliopathies, a diverse group of disorders often affecting skeletal development. This includes Jeune syndrome or asphyxiating thoracic dystrophy (ATD), an autosomal recessive skeletal disorder. Unraveling the responsible molecular pathology helps illuminate mechanisms responsible for functional primary cilia. We identified two families withATDcaused by loss-of-function mutations in the gene encoding adrenergic receptor kinase 1 (ADRBK1orGRK2).GRK2cells from an affected individual homozygous for the p.R158* mutation resulted in loss ofGRK2, and disrupted chondrocyte growth and differentiation in the cartilage growth plate.GRK2null cells displayed normal cilia morphology, yet loss ofGRK2 compromised cilia-based signaling of Hedgehog (Hh) pathway. Canonical Wnt signaling was also impaired, manifested as a failure to respond to Wnt ligand due to impaired phosphorylation of the Wnt co-receptorLRP6. We have identifiedGRK2 as an essential regulator of skeletogenesis and demonstrate how both Hh and Wnt signaling mechanistically contribute to skeletal ciliopathies.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10603 - Genetics and heredity (medical genetics to be 3)

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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