Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F20%3AN0000214" target="_blank" >RIV/00027162:_____/20:N0000214 - isvavai.cz</a>
Alternative codes found
RIV/67985904:_____/20:00536280 RIV/00216224:14110/20:00114425 RIV/00159816:_____/20:00073506
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>
Alternative languages
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 with ATD caused by loss-of-function mutations in the gene encoding adrenergic receptor kinase 1 (ADRBK1 or GRK2). GRK2 cells from an affected individual homozygous for the p.R158* mutation resulted in loss of GRK2, and disrupted chondrocyte growth and differentiation in the cartilage growth plate. GRK2 null cells displayed normal cilia morphology, yet loss of GRK2 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-receptor LRP6. We have identified GRK2 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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Classification
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
30101 - Human genetics
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EMBO Molecular Medicine
ISSN
1757-4676
e-ISSN
1757-4684
Volume of the periodical
12
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
"e11739"
UT code for WoS article
000577616000001
EID of the result in the Scopus database
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