Destabilization of the IFT-B cilia core complex due to mutations in IFT81 causes a Spectrum of Short-Rib Polydactyly Syndrome
| Autor: | Rhonda P. Spiro, Daniel H. Cohn, S. Paige Taylor, Jorge H. Martin, Michael J. Bamshad, Kimberly N. Forlenza, Wenjuan Zhang, Deborah Krakow, Ivan Duran, Deborah A. Nickerson |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetics Multidisciplinary Short rib – polydactyly syndrome biology Polydactyly Cilium Mutant medicine.disease Ciliopathies Hedgehog signaling pathway Article Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Tubulin biology.protein Axoplasmic transport medicine sense organs 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep34232 |
| Popis: | Short-rib polydactyly syndromes (SRPS) and Asphyxiating thoracic dystrophy (ATD) or Jeune Syndrome are recessively inherited skeletal ciliopathies characterized by profound skeletal abnormalities and are frequently associated with polydactyly and multiorgan system involvement. SRPS are produced by mutations in genes that participate in the formation and function of primary cilia and usually result from disruption of retrograde intraflagellar (IFT) transport of the cilium. Herein we describe a new spectrum of SRPS caused by mutations in the gene IFT81, a key component of the IFT-B complex essential for anterograde transport. In mutant chondrocytes, the mutations led to low levels of IFT81 and mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components. These findings demonstrate the importance of IFT81 in the skeleton, its role in the anterograde transport complex, and expand the number of loci associated with SRPS. |
| Databáze: | OpenAIRE |
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