Circadian clock regulation of the glycogen synthase (gsn) gene by WCC is critical for rhythmic glycogen metabolism in Neurospora crassa

Author(s):Show less -

Baek, Mokryun ^[1] ; Virgilio, Stela ^[2] ; Lamb, Teresa M. ^[3] ; Ibarra, Oneida ^[3] ; Andrade, Juvana Moreira ^[2] ; Goncalves, Rodrigo Duarte ^[2] ; Dovzhenok, Andrey ^[4] ; Lim, Sookkyung ^[4] ; Bell-Pedersen, Deborah ^[3] ; Bertolini, Maria Celia ^[2] ; Hong, Christian I. ^{[1, 5]}

Affiliation

^[1] Univ Cincinnati, Dept Pharmacol & Syst Physiol, Cincinnati, OH 45267 - USA

^[2] Univ Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, BR-14800060 Araraquara, SP - Brazil

^[3] Texas A&M Univ, Dept Biol, College Stn, TX 77843 - USA

^[4] Univ Cincinnati, Dept Math Sci, Cincinnati, OH 45221 - USA

^[5] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Dev Biol, Cincinnati, OH 45229 - USA

• Document type: Journal article
• Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 116, n. 21, p. 10435-10440, MAY 21 2019.
• Web of Science Citations: 0

Abstract

Circadian clocks generate rhythms in cellular functions, including metabolism, to align biological processes with the 24-hour environment. Disruption of this alignment by shift work alters glucose homeostasis. Glucose homeostasis depends on signaling and allosteric control; however, the molecular mechanisms linking the clock to glucose homeostasis remain largely unknown. We investigated the molecular links between the clock and glycogen metabolism, a conserved glucose homeostatic process, in Neurospora crassa. We find that glycogen synthase (gsn) mRNA, glycogen phosphorylase (gpn) mRNA, and glycogen levels, accumulate with a daily rhythm controlled by the circadian clock. Because the synthase and phosphorylase are critical to homeostasis, their roles in generating glycogen rhythms were investigated. We demonstrate that while gsn was necessary for glycogen production, constitutive gsn expression resulted in high and arrhythmic glycogen levels, and deletion of gpn abolished gsn mRNA rhythms and rhythmic glycogen accumulation. Furthermore, we show that gsn promoter activity is rhythmic and is directly controlled by core clock component white collar complex (WCC). We also discovered that WCC-regulated transcription factors, VOS-1 and CSP-1, modulate the phase and amplitude of rhythmic gsn mRNA, and these changes are similarly reflected in glycogen oscillations. Together, these data indicate the importance of clock-regulated gsn transcription over signaling or allosteric control of glycogen rhythms, a mechanism that is potentially conserved in mammals and critical to metabolic homeostasis. (AU)

• FAPESP's process: 13/14513-0 - Connection studies between biological clock and glycogen metabolism regulation in Neurospora crassa
• Grantee: Stela Virgilio
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/24705-3 - The filamentous fungus Neurospora crassa as a model organism for the functional characterization of proteins/transcription factors that regulate the carbohydrate metabolism
• Grantee: Maria Celia Bertolini
• Support Opportunities: Research Projects - Thematic Grants