Autor según el artículo: 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
Departamento: Enginyeria Electrònica, Elèctrica i Automàtica
Autor/es de la URV: Junza Martínez, Alexandra / Yanes Torrado, Óscar
Palabras clave: 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
Resumen: © 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.
Áreas temáticas: 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
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 2050-084X
Direcció de correo del autor: oscar.yanes@urv.cat alexandra.junza@urv.cat
Identificador del autor: 0000-0003-3695-7157 0000-0001-7205-0419
Fecha de alta del registro: 2024-10-12
Volumen de revista: 9
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://elifesciences.org/articles/56418
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Elife. 9 e56418-
Referencia de l'ítem segons les normes 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
DOI del artículo: 10.7554/eLife.56418
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2020
Tipo de publicación: Journal Publications
Repositori URV