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Consalvo, K. M.

Publications and source records attributed to Consalvo, K. M..

2 recordsLinked to original sources

Differences between human male and female neutrophils with respect to which RNAs are present in polysomes

BackgroundHuman males and females show differences in the incidence of neutrophil-associated diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis, and differences in neutrophil physiological responses such as responses to infection, tissue damage, and chemotactic factors. However, little is known about the basis of sex-based differences in human neutrophils. MethodsStarting with human neutrophils from healthy donors, we used RNA-seq to examine total RNA profiles, RNAs not associated with ribosomes and thus not being translated, RNAs in monosomes, and RNAs in polysomes and thus heavily translated. ResultsThere were sex-based differences in the levels of RNAs across free RNA, monosome, and polysome fractions. Male neutrophils had increased levels of mRNAs encoding mitochondrial proteins in the free RNA fractions, indicating low levels of translation. The polysomes of male neutrophils were enriched for mRNAs encoding cytoskeletal organization, cell motility, and cell activation. The polysomes of female neutrophils were enriched for mRNAs associated the regulation of metabolic processes, cytokine responses, and mitochondrial proteins. ConclusionsThese data indicate that male and female neutrophils have different expression patterns and different translation efficiency of some mRNAs. This may contribute to the observed sex-based differences in neutrophil behavior and neutrophil-associated disease incidence and severity.

immunology↗

PTEN and the PTEN-like phosphatase CnrN have both distinct and overlapping roles in a Dictyostelium chemorepulsion pathway

The directed movement of eukaryotic cells is crucial for processes such as embryogenesis and immune cell trafficking. The enzyme Phosphatase and tensin homolog (PTEN) dephosphorylates phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] to phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Dictyostelium discoideum cells require both PTEN and the PTEN-like phosphatase CnrN to locally inhibit Ras activation to induce biased movement of cells away from the secreted chemorepellent protein AprA. Both PTEN and CnrN decrease basal levels of PI(3,4,5)P3 and increase basal numbers of macropinosomes, and AprA prevents this increase. AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels, decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II phosphorylation, and increase filopod sizes. AprA causes PTEN, similar to CnrN, to localize to the side of the cell towards AprA in an AprA gradient. However, PTEN and CnrN also have distinct roles in some signaling pathways. PTEN, but not CnrN, decreases basal levels of PI(4,5)P2, AprA requires PTEN, but not CnrN, to induce cell roundness, and CnrN and PTEN have different effects on the number of filopods and pseudopods, and the sizes of filopods. Together, our results suggest that CnrN and PTEN play unique roles in D. discoideum signaling pathways, and possibly dephosphorylate PI(3,4,5)P3 in different membrane domains, to mediate chemorepulsion away from AprA.

cell biology↗