Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/173074
Title: Post-translational regulation of retinal IMPDH1 in vivo to adjust GTP synthesis to illumination conditions
Author: Plana-Bonamaisó, Anna
López Begines, Santiago
Fernández Justel, David
Junza, Alexandra
Soler Tapia, Ariadna
Andilla, Jordi
Loza Alvarez, Pablo
Rosa López, José Luis
Miralles, Esther
Casals, Isidre
Yanes, Oscar
Villa, Pedro de la
Buey, Ruben M.
Méndez Zunzunegui, Ana
Keywords: Homeòstasi
Nucleòtids
Homeostasis
Nucleotides
Issue Date: 7-Apr-2020
Publisher: Elife Sciences Publications Ltd.
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.7554/eLife.56418
It is part of: Elife, 2020, vol. 9
URI: http://hdl.handle.net/2445/173074
Related resource: https://doi.org/10.7554/eLife.56418
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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