Author, as appears in the article.: Plana-Bonamaiso, Anna; Lopez-Begines, Santiago; Fernandez-Justel, David; Junza, Alexandra; Soler-Tapia, Ariadna; Andilla, Jordi; Loza-Alvarez, Pablo; Luis Rosa, Jose; Miralles, Esther; Casals, Isidre; Yanes, Oscar; de la Villa, Pedro; Buey, Ruben M; Mendez, Ana
Department: Enginyeria Electrònica, Elèctrica i Automàtica
URV's Author/s: Junza Martínez, Alexandra / Yanes Torrado, Óscar
Keywords: Rod Rhodopsin Retinal dystrophy Photoreceptor cells Mutations Multiple phosphorylation Kinase Identification Dominant retinitis-pigmentosa Dehydrogenase type-1 Acid photoreceptor physiology photoreceptor metabolism neuroscience mouse impdh1 enzymology chemical biology cgmp biochemistry
Abstract: © Plana-Bonamaisó et al. 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.
Thematic Areas: Saúde coletiva Química Nutrição Neuroscience (miscellaneous) Neuroscience (all) Medicine (miscellaneous) Medicina veterinaria Medicina ii Medicina i Interdisciplinar Immunology and microbiology (miscellaneous) Immunology and microbiology (all) Geografía Geociências General neuroscience General medicine General immunology and microbiology General biochemistry,genetics and molecular biology Farmacia Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Biotecnología Biology Biodiversidade Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Astronomia / física
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 2050-084X
Author's mail: oscar.yanes@urv.cat alexandra.junza@urv.cat
Author identifier: 0000-0003-3695-7157 0000-0001-7205-0419
Record's date: 2024-10-12
Journal volume: 9
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://elifesciences.org/articles/56418
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Elife. 9 e56418-
APA: Plana-Bonamaiso, Anna; Lopez-Begines, Santiago; Fernandez-Justel, David; Junza, Alexandra; Soler-Tapia, Ariadna; Andilla, Jordi; Loza-Alvarez, Pablo; (2020). Post-translational regulation of retinal IMPDH1 in vivo to adjust GTP synthesis to illumination conditions. Elife, 9(), e56418-. DOI: 10.7554/eLife.56418
Article's DOI: 10.7554/eLife.56418
Entity: Universitat Rovira i Virgili
Journal publication year: 2020
Publication Type: Journal Publications
Repositori URV