A new role for human dyskerin in vesicular trafficking
| Autor: | Maria Furia, Valentina Belli, Mimmo Turano, Alberto Angrisani, Rosario Vicidomini, Nunzia Di Maio |
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| Přispěvatelé: | DI MAIO, Nunzia, Vicidomini, Rosario, Angrisani, Alberto, Belli, Valentina, Furia, Maria, Turano, Mimmo |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Gene knockdown Nucleolus Rab5/Rab11 endosomes Endocytic cycle Biology medicine.disease DKC1 Phenotype General Biochemistry Genetics and Molecular Biology Dyskerin Telomere Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis medicine cytoskeletal remodeling Dyskeratosis congenita Loss function Research Articles Research Article |
| Zdroj: | FEBS Open Bio |
| ISSN: | 2211-5463 |
| Popis: | Dyskerin is an essential, conserved, multifunctional protein found in the nucleolus, whose loss of function causes the rare genetic diseases X-linked dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. To further investigate the wide range of dyskerin's biological roles, we set up stable cell lines able to trigger inducible protein knockdown and allow a detailed analysis of the cascade of events occurring within a short time frame. We report that dyskerin depletion quickly induces cytoskeleton remodeling and significant alterations in endocytic Ras-related protein Rab-5A/Rab11 trafficking. These effects arise in different cell lines well before the onset of telomere shortening, which is widely considered the main cause of dyskerin-related diseases. Given that vesicular trafficking affects many homeostatic and differentiative processes, these findings add novel insights into the molecular mechanisms underlining the pleiotropic manifestation of the dyskerin loss-of-function phenotype. |
| Databáze: | OpenAIRE |
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