دورية أكاديمية
Post-translational regulation of retinal IMPDH1 in vivo to adjust GTP synthesis to illumination conditions
| العنوان: | Post-translational regulation of retinal IMPDH1 in vivo to adjust GTP synthesis to illumination conditions |
|---|---|
| المؤلفون: | Anna Plana-Bonamaisó, Santiago López-Begines, David Fernández-Justel, Alexandra Junza, Ariadna Soler-Tapia, Jordi Andilla, Pablo Loza-Alvarez, Jose Luis Rosa, Esther Miralles, Isidre Casals, Oscar Yanes, Pedro de la Villa, Ruben M Buey, Ana Méndez |
| المصدر: | eLife, Vol 9 (2020) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | retinal dystrophy, photoreceptor metabolism, IMPDH1, enzymology, photoreceptor physiology, cGMP, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | We report the in vivo regulation of Inosine-5´-monophosphate dehydrogenase 1 (IMPDH1) in the retina. IMPDH1 catalyzes the rate-limiting step in the de novo synthesis of guanine nucleotides, impacting the cellular pools of GMP, GDP and GTP. Guanine nucleotide homeostasis is central to photoreceptor cells, where cGMP is the signal transducing molecule in the light response. Mutations in IMPDH1 lead to inherited blindness. We unveil a light-dependent phosphorylation of retinal IMPDH1 at Thr159/Ser160 in the Bateman domain that desensitizes the enzyme to allosteric inhibition by GDP/GTP. When exposed to bright light, living mice increase the rate of GTP and ATP synthesis in their retinas; concomitant with IMPDH1 aggregate formation at the outer segment layer. Inhibiting IMPDH activity in living mice delays rod mass recovery. We unveil a novel mechanism of regulation of IMPDH1 in vivo, important for understanding GTP homeostasis in the retina and the pathogenesis of adRP10 IMPDH1 mutations. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/56418Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.56418 |
| الوصول الحر: | https://doaj.org/article/0bb5adc61dcb4789b7eeb46936f8f9d9Test |
| رقم الانضمام: | edsdoj.0bb5adc61dcb4789b7eeb46936f8f9d9 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
|---|---|
| DOI: | 10.7554/eLife.56418 |