| Autor: |
Milosavljevic, Julian, Lempicki, Camille, Lang, Konrad, Heinkele, Helena, Kampf, Lina L., Leroy, Claire, Chen, Mengmeng, Gerstner, Lea, Spitz, Dominik, Wang, Minxian, Knob, Andrea U., Kayser, Séverine, Helmstädter, Martin, Walz, Gerd, Pollak, Martin R., Hermle, Tobias |
| Zdroj: |
Journal of the American Society of Nephrology; December 2022, Vol. 33 Issue: 12 p2174-2193, 20p |
| Abstrakt: |
Variants in TBC1D8Bcause isolated nephrotic syndrome. TBC1D8B protein interacts with the slit diaphragm protein nephrin, but the pathogenesis remains unclear. We used Drosophilato elucidate the functional role of the recently discovered disease-causing gene. A null allele of Tbc1d8bin Drosophilaexhibits a nephrocyte-restricted phenotype similar to patient presentation. Tbc1d8b protein localizes to mature early and late endosomes and promotes endosomal maturation and degradation, and is further required for nephrin transport. Expression of the murine ortholog rescues loss-of-function of the Drosophila TBC1D8B,which indicates evolutionary conservation. Discovery of two novel variants in TBC1D8Bin a cohort of 363 patients with FSGS and functional validation in Drosophilasuggest that TBC1D8Bvariants significantly underlie hereditary FSGS. |
| Databáze: |
Supplemental Index |
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