Flux 7.1.11

Flux 7.1.11

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Most large-scale biological processes, like global element cycling or decomposition of organic matter, are mediated by microbial consortia. Commonly, the different species in such consortia exhibit mutual metabolic dependencies that include the exchange of nutrients. Despite the global importance, surprisingly little is known about the metabolic interplay between species in particular subpopulations. To gain insight into the intracellular fluxes of subpopulations and their interplay within such mixed cultures, we developed here a (13)C flux analysis approach based on affinity purification of the recombinant fusion glutathione S-transferase (GST) and green fluorescent protein (GFP) as a reporter protein. Instead of detecting the (13)C labeling patterns in the typically used amino acids from the total cellular protein, our method detects these (13)C patterns in amino acids from the reporter protein that has been expressed in only one species of the consortium. As a proof of principle, we validated our approach by mixed-culture experiments of an Escherichia coli wild type with two metabolic mutants. The reporter method quantitatively resolved the expected mutant-specific metabolic phenotypes down to subpopulation fractions of about 1%.

The strong expression of ATP-gated P2X3 receptors by a subpopulation of sensory neurons indicates the important role of these membrane proteins in nociceptive signaling in health and disease, especially when the latter is accompanied by chronic pain syndromes. These receptors exist mainly as trimeric homomers, and, in part, as heteromers (assembly of two P2X3 subunits with one P2X2). Recent investigations have suggested distinct molecular determinants responsible for agonist binding and channel opening for transmembrane flux of sodium, calcium and potassium ions. Trimeric P2X3 receptors are rapidly activated by ATP and can be strongly desensitized in the continuous presence of the agonist. Endogenous substances, widely thought to be involved in triggering pain, especially in pathological conditions, can potently modulate the expression and function of P2X3 receptors, with differential changes in response amplitude, desensitization and recovery. Strong facilitation of P2X3 receptor function is induced by enodogenous substances like the neuropeptide calcitonin gene-related peptide and the neurotrophins nerve growth factor and brain-derived neurotrophic factor. These substances possess distinct mechanisms of action on P2X3 receptors, generally attributable to discrete phosphorylation of N- or C-terminal P2X3 domains (Fabbretti and Nistri, 2012).

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Meng, N.N. Song, L. Chen, Y.C. Kim, J. Chen, and W.X. Xu. (2019). Diabetes-induced damage of gastric nitric oxide neurons mediated by P2X7R in diabetic mice. Eur J Pharmacol 851: 151-160. [Epub: Ahead of Print]Examples:TC#NameOrganismal TypeExample1.A.7.1.1ATP-gated cation channel (purinoceptor or ATP-neuroreceptor). Residues Glu52-Gly96 play roles in agonist binding and channel gating (Allsopp et al., 2011). The rat protein is 89% identical to the human ortholog. Mutations likely to confer ivermectin sensitivity to human P2X1 have been proposed (Pasqualetto et al. 2018). 2b1af7f3a8