Regulatory phosphorylation site tunes Phosphoglucomutase 1 as a metabolic valve to control mobilization of glycogen stores

Abstract:

Regulation of glycogen metabolism is of vital importance in organisms of all three kingdoms of life. Although the pathways involved in glycogen synthesis and degradation are well known, many regulatory aspects around the metabolism of this polysaccharide remain undeciphered. Here, we used the unicellular cyanobacterium Synechocystis as a model to investigate how glycogen metabolism is regulated in dormant nitrogen-starved cells, which entirely rely on glycogen catabolism to restore growth. We found that the activity of the enzymes involved in glycogen synthesis and degradation is tightly controlled at different levels via post-translational modifications. Phosphorylation of phosphoglucomutase 1 (Pgm1) on a peripheral residue (Ser63) regulates Pgm1 activity and controls the mobilization of the glycogen stores. Inhibition of Pgm1 activity via phosphorylation on Ser63 appears essential for survival of Synechocystis in the dormant state. Remarkably, this regulatory mechanism seems to be conserved from bacteria to humans. Moreover, phosphorylation of Pgm1 influences the formation of a metabolon, which includes Pgm1, oxidative pentose phosphate cycle protein (OpcA) and glucose-6-phosphate dehydrogenase (G6PDH). Analysis of the steady-state levels of the metabolic products of glycogen degradation together with protein-protein interaction studies revealed that the activity of G6PDH and the formation of this metabolon are under additional redox control, likely to ensure metabolic channeling of glucose-6-phosphate to the required pathways for each developmental stage.

Citation: biorxiv;2021.04.15.439997v1,[Preprint]

Date Published: 15th Apr 2021

Registered Mode: by DOI

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Citation
Doello, S., Neumann, N., Spät, P., Maček, B., & Forchhammer, K. (2021). Regulatory phosphorylation site tunes Phosphoglucomutase 1 as a metabolic valve to control mobilization of glycogen stores. In []. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2021.04.15.439997
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Created: 6th Jun 2021 at 18:35

Last updated: 6th Jun 2021 at 18:36

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