Articles producció científica> Enginyeria Electrònica, Elèctrica i Automàtica

Post-translational regulation of retinal IMPDH1 in vivo to adjust GTP synthesis to illumination conditions

  • Dades identificatives

    Identificador: imarina:6389880
    Autors:
    Plana-Bonamaiso, AnnaLopez-Begines, SantiagoFernandez-Justel, DavidJunza, AlexandraSoler-Tapia, AriadnaAndilla, JordiLoza-Alvarez, PabloLuis Rosa, JoseMiralles, EstherCasals, IsidreYanes, Oscarde la Villa, PedroBuey, Ruben MMendez, Ana
    Resum:
    © 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.
  • Altres:

    Autor segons l'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
    Departament: Enginyeria Electrònica, Elèctrica i Automàtica
    Autor/s de la URV: Junza Martínez, Alexandra / Yanes Torrado, Óscar
    Paraules clau: 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
    Resum: © 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.
    Àrees temàtiques: 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
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 2050-084X
    Adreça de correu electrònic de l'autor: oscar.yanes@urv.cat alexandra.junza@urv.cat
    Identificador de l'autor: 0000-0003-3695-7157 0000-0001-7205-0419
    Data d'alta del registre: 2024-10-12
    Volum de revista: 9
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://elifesciences.org/articles/56418
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Elife. 9 e56418-
    Referència 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 de l'article: 10.7554/eLife.56418
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2020
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Biochemistry, Genetics and Molecular Biology (Miscellaneous),Biology,Immunology and Microbiology (Miscellaneous),Medicine (Miscellaneous),Neuroscience (Miscellaneous)
    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
    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
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