Australia is famous, among other things, for venomous animals. Its plants, it turns out, are just as hostile. Now, researchers at the University of Queensland have isolated “neurotoxic peptides from the venom of the giant Australian stinging tree,” as they titled their paper. While the tree’s venomous effects were no secret – the authors wrote that it is known for its “remarkably persistent and painful stings upon contact,” which can produce pain flares for weeks – the effect had been attributed to small molecules. The researchers showed that the tree also produces peptides that strongly activated pain sensations. The researchers named the peptide class gympietides, after the stinging tree’s botanical name of “Gympie Gympie,” and showed that their structure was similar to that of cone snail and spider toxins, an example of inter-kingdom convergent evolution. Cone snail and spider venoms are the basis of attempts to develop new classes of analgesics, and the gympietides may also have potential in that regard. The study appeared in the Sept. 16, 2020, issue of Science Advances.
Glial metabolism affects neural recovery
Investigators at Temple University and the Children’s Hospital of Philadelphia have discovered a link between glial metabolism and neuronal regeneration, or the lack thereof, after spinal cord injury. The adult central nervous system (CNS) of most vertebrates does not regenerate after injury, which is due in part to the formation of a glial scar by astrocytes. In their experiments, the team showed that this inhibitory effect depended on the metabolic status of the astrocytes. Increased glycolysis produced the metabolites L-lactate and L-2-hydroxyglutarate (L-2HG), which could induce regeneration of axons in fruit flies by activating GABA receptors and, ultimately, PI3K and EGFR pathways. Combined activation of those pathways in glial cells “drastically converted the inhibitory environment and unprecedented elongation of axon regrowth in the CNS was observed” in fruit flies, the authors wrote. “Local application of L-lactate to injured spinal cord promoted corticospinal tract axon regeneration, leading to behavioral recovery in adult mice.” They reported their results in the Sept. 16, 2020, online issue of Cell Metabolism.
A tense defense
Researchers at the University of Cambridge and the KEMRI Wellcome Trust Research Program have demonstrated that red blood cells expressing a specific surface protein, the Dantu antigen, had higher tension than average red blood cells (RBCs). That increased tension protected RBCs from invasion by the malaria parasite Plasmodium falciparum. Mice with Dantu-expressing RBCs, in turn, were protected against severe malaria. Dantu is the result of a rearrangement of two proteins, glycophorin A and glycophorin B, that are both important for P. falciparum infection of RBCs. The Dantu polymorphism is a known protective factor against malaria, and in some malaria-endemic areas, it is as frequent as the sickle cell trait. The authors showed that possession of the Dantu polymorphism by RBCs was “associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC-parasite receptor-ligand interactions.” Instead, it raised the tension of the RBCs with the polymorphism. Membrane tension varies naturally between cells, and cells with high tension that did not express Dantu were also protected against malaria infection. The team published its findings in the Sept. 17, 2020, issue of Nature.