Adenylosuccinate Lyase activity in the Purine recycling pathway is essential for developmental timing, germline maintenance and muscle integrity in C. elegans
Adenylosuccinate Lyase activity in the Purine recycling pathway is essential for developmental timing, germline maintenance and muscle integrity in C. elegans
Abstract Purine homeostasis is ensured through a metabolic network widely conserved from prokaryotes to humans. Purines can either be synthesized de novo, reused, or produced by interconversion of extant metabolites using the so-called recycling pathway. Although thoroughly characterized in microorganisms, such as yeast or bacteria, little is known about the regulation of this biosynthesis network in metazoans. In humans, several diseases are linked to purine biosynthesis deficiencies through yet poorly understood etiologies. Particularly, the deficiency in Adenylosuccinate Lyase (ADSL), one enzyme involved both in the purine de novo and recycling pathways, causes severe muscular and neuronal symptoms. In order to address the mechanisms underlying this deficiency, we established Caenorhabditis elegans as a metazoan model organism to study purine metabolism, while focusing on ADSL. We show that the purine biosynthesis network is functionally conserved in C. elegans. Moreover, ADSL is required for developmental timing and germline stem cell maintenance, and muscle integrity. Our results allow to ascribe developmental and tissue specific phenotypes to separable steps of the purine metabolic network in an animal model. Particularly, the muscle, germline and developmental defects are linked specifically to the ADSL role in the purine recycling pathway.
ArtalSanz Marta、Gomes Jos¨|-Eduardo、Marsac Roxane、Olmedo Mar¨aa、Saint-Marc Christelle、Daignan-Fornier Bertrand、Pinson Beno?t
Andalusian Center for Developmental Biology, Consejo Superior de Investigaciones Cient¨aficas/Junta de Andaluc¨aa/Universidad Pablo de Olavide, Department of Molecular Biology and Biochemical EngineeringInstitut de Biochimie et G¨|n¨|tique Cellulaires, Universit¨| de Bordeaux and CNRS UMR5095Institut de Biochimie et G¨|n¨|tique Cellulaires, Universit¨| de Bordeaux and CNRS UMR5095Andalusian Center for Developmental Biology, Consejo Superior de Investigaciones Cient¨aficas/Junta de Andaluc¨aa/Universidad Pablo de Olavide, Department of Molecular Biology and Biochemical EngineeringInstitut de Biochimie et G¨|n¨|tique Cellulaires, Universit¨| de Bordeaux and CNRS UMR5095Institut de Biochimie et G¨|n¨|tique Cellulaires, Universit¨| de Bordeaux and CNRS UMR5095Institut de Biochimie et G¨|n¨|tique Cellulaires, Universit¨| de Bordeaux and CNRS UMR5095
生物化学遗传学分子生物学
ArtalSanz Marta,Gomes Jos¨|-Eduardo,Marsac Roxane,Olmedo Mar¨aa,Saint-Marc Christelle,Daignan-Fornier Bertrand,Pinson Beno?t.Adenylosuccinate Lyase activity in the Purine recycling pathway is essential for developmental timing, germline maintenance and muscle integrity in C. elegans[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/277640.点此复制
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