Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/621957
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AbstractThe storage and use of glycogen, the main energy reserve in the brain, is a metabolic feature of astrocytes. Glycogen synthesis is regulated by Protein Targeting to Glycogen (PTG), a member of specific glycogen-binding subunits of protein phosphatase-1 (PPP1). It positively regulates glycogen synthesis through de-phosphorylation of both glycogen synthase (activation) and glycogen phosphorylase (inactivation). In cultured astrocytes, PTG mRNA levels were previously shown to be enhanced by the neurotransmitter noradrenaline. To achieve further insight into the role of PTG in the regulation of astrocytic glycogen, its levels of expression were manipulated in primary cultures of mouse cortical astrocytes using adenovirus-mediated overexpression of tagged-PTG or siRNA to downregulate its expression. Infection of astrocytes with adenovirus led to a strong increase in PTG expression and was associated with massive glycogen accumulation (>100 fold), demonstrating that increased PTG expression is sufficient to induce glycogen synthesis and accumulation. In contrast, siRNA-mediated downregulation of PTG resulted in a 2-fold decrease in glycogen levels. Interestingly, PTG downregulation strongly impaired long-term astrocytic glycogen synthesis induced by insulin or noradrenaline. Finally, these effects of PTG downregulation on glycogen metabolism could also be observed in cultured astrocytes isolated from PTG-KO mice. Collectively, these observations point to a major role of PTG in the regulation of glycogen synthesis in astrocytes and indicate that conditions leading to changes in PTG expression will directly impact glycogen levels in this cell type.
CitationRuchti E, Roach PJ, DePaoli-Roach AA, Magistretti PJ, Allaman I (2016) Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes. IBRO Reports 1: 46–53. Available: http://dx.doi.org/10.1016/j.ibror.2016.10.002.
SponsorsThe authors would like to thank Elena Gasparotto for expert technical assistance, Dr. Sylvain Lengacher for initial work on PTG adenoviral overexpression and Dr. Gabriele Grenningloh for critical reading of the manuscript. This work was supported by grants from Swiss National Science Foundation (FNRS) (grant numbers 31003A_130821 and 310030B_148169) and from the Panacée and Préfargier Foundations to PJM. The PTG knockout mice were supported by NIH grants DK27221 and NS056454 to PJR.
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