Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes
| Autor: | E. Ruchti, Anna A. DePaoli-Roach, Igor Allaman, Peter J. Roach, Pierre J. Magistretti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cell type medicine.medical_treatment Carbohydrate metabolism Article lcsh:RC321-571 03 medical and health sciences chemistry.chemical_compound Glycogen phosphorylase 0302 clinical medicine Downregulation and upregulation Internal medicine Glia medicine Insulin Neurotransmitter Glycogen synthase Ins Insulin lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Glucose metabolism biology Glycogen NA Noradrenaline General Neuroscience PTG Protein targeting to glycogen GS Glycogen synthase 030104 developmental biology Endocrinology chemistry biology.protein Noradrenaline GP Glycogen phosphorylase 030217 neurology & neurosurgery |
| Zdroj: | IBRO Reports IBRO Reports, Vol 1, Iss C, Pp 46-53 (2016) |
| ISSN: | 2451-8301 |
| Popis: | The 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. |
| Databáze: | OpenAIRE |
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