Glycogen-targeting PP1 (protein phosphatase 1) subunit GL (coded for by the PPP1R3B gene) is expressed in human, but not rodent, skeletal muscle. Its effects on muscle glycogen metabolism are unknown. We show that GL mRNA levels in primary cultured human myotubes are similar to those in freshly excised muscle, unlike subunits GM (gene PPP1R3A) or PTG (protein targeting to glycogen; gene PPP1R3C), which decrease strikingly. In cultured myotubes, expression of the genes coding for GL, GM and PTG is not regulated by glucose or insulin. Overexpression of GL activates myotube GS (glycogen synthase), glycogenesis in glucose-replete and -depleted cells and glycogen accumulation. Compared with overexpressed GM, GL has a more potent activating effect on glycogenesis, while marked enhancement of their combined action is only observed in glucose-replete cells. GL does not affect GP (glycogen phosphorylase) activity, while co-overexpression with muscle GP impairs GL activation of GS in glucose-replete cells. GL enhances long-term glycogenesis additively to glucose depletion and insulin, although GL does not change the phosphorylation of GSK3 (GS kinase 3) on Ser9 or its upstream regulator kinase Akt/protein kinase B on Ser473, nor its response to insulin. In conclusion, in cultured human myotubes, the GL gene is expressed as in muscle tissue and is unresponsive to glucose or insulin, as are GM and PTG genes. GL activates GS regardless of glucose, does not regulate GP and stimulates glycogenesis in combination with insulin and glucose depletion.
Expression and glycogenic effect of glycogen-targeting protein phosphatase 1 regulatory subunit GL in cultured human muscle
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Marta Montori-Grau, Maria Guitart, Carles Lerin, Antonio L. Andreu, Christopher B. Newgard, Cèlia García-Martínez, Anna M. Gómez-Foix; Expression and glycogenic effect of glycogen-targeting protein phosphatase 1 regulatory subunit GL in cultured human muscle. Biochem J 1 July 2007; 405 (1): 107–113. doi: https://doi.org/10.1042/BJ20061572
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