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Dagenais, A.

Publications and source records attributed to Dagenais, A..

2 recordsLinked to original sources

Identification of polyphosphate-binding proteins in E. coli uncovers targets involved in translation control and ribosome biogenesis

In many bacteria, polyphosphate kinase (PPK) enzymes use ATP to synthesize polyphosphate (polyP) in response to cellular stress. These chains of inorganic phosphates are joined by high-energy bonds and can reach hundreds of residues in length. PolyP plays diverse functions in helping bacteria adjust to changing environmental conditions. However, the molecular mechanisms underlying these functions are poorly understood. In eukaryotic cells, polyacidic serine- and lysine-rich (PASK) motifs of proteins can mediate binding to polyP chains. Whereas PASK motifs are relatively common in yeast and human cells, we report that these sequences are rare in bacteria commonly used for polyP research. Thus, to identify novel polyP-binding proteins in Escherichia coli, we carried out an untargeted screen and identified 7 novel targets with links to translation control and ribosome biogenesis. For two targets, the GTPase activating protein YihI and the ribonuclease Rnr, we mapped the regions of polyP interaction to non-PASK sequences and identified lysine residues critical for binding. We found that deletion of rnr suppressed the slow growth phenotype of {Delta}ppk mutants grown on minimal media. Conversely, ppk deletion resulted in decreased Rnr protein expression. These phenotypes were dependent on the polyP binding region of Rnr but independent of polyP binding itself, suggesting a complex interplay between PPK and Rnr function in E. coli. Overall, our work provides new insights into the scope of polyP binding proteins and extends the connections between polyP and the regulation of protein translation in E. coli.

molecular biology↗

Interleukin-10-producing monocytes contribute to sex differences in pain resolution in mice and humans.

Pain is closely associated with the immune system, which exhibits sexual dimorphism. For these reasons, neuro-immune interactions are suggested to drive sex differences in pain pathophysiology. However, our understanding of peripheral neuro-immune interactions on sex differences in pain resolution remains limited. Here, we have shown, in both a mouse model of inflammatory pain and in humans following traumatic pain, that males had higher levels of interleukin (IL)-10 than females, which were correlated with faster pain resolution. Following injury, we identified monocytes (CD11b+ Ly6C+ Ly6G-F4/80mid) as the primary source of IL-10, with IL-10-producing monocytes being more abundant in males than females. In a mouse model, neutralizing IL-10 signaling through antibodies, genetically ablating IL-10R1 in sensory neurons, or depleting monocytes with clodronate all impaired the resolution of pain hypersensitivity in both sexes. Furthermore, manipulating androgen levels in mice reversed the sexual dimorphism of pain resolution and the levels of IL-10-producing monocytes. These results highlight a novel role for androgen-driven peripheral IL-10-producing monocytes in the sexual dimorphism of pain resolution. These findings add to the growing concept that immune cells play a critical role in resolving pain and preventing the transition into chronic pain. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/565129v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@6e158corg.highwire.dtl.DTLVardef@148c8b5org.highwire.dtl.DTLVardef@1711d2dorg.highwire.dtl.DTLVardef@132a755_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗