Glycogen Synthase Kinase-3 is involved in glycogen metabolism control and embryogenesis of Rhodnius prolixus

Abstract

Rhodnius prolixus is a blood-feeding insect that transmits Trypanosoma cruzi and Trypanosoma rangeli to vertebrate hosts. Rhodnius prolixus is also a classical model in insect physiology, and the recent availability of R. prolixus genome has opened new avenues on triatomine research. Glycogen synthase kinase 3 (GSK-3) is classically described as a key enzyme involved in glycogen metabolism, also acting as a downstream component of the Wnt pathway during embryogenesis. GSK-3 has been shown to be highly conserved among several organisms, mainly in the catalytic domain region. Meanwhile, the role of GSK-3 during R. prolixus embryogenesis or glycogen metabolism has not been investigated. Here we show that chemical inhibition of GSK-3 by alsterpaullone, an ATP-competitive inhibitor of GSK3, does not affect adult survival rate, though it alters oviposition and egg hatching. Specific GSK-3 gene silencing by dsRNA injection in adult females showed a similar phenotype. Furthermore, bright field and 4'-6-diamidino-2-phenylindole (DAPI) staining analysis revealed that ovaries and eggs from dsGSK-3 injected females exhibited specific morphological defects. We also demonstrate that glycogen content was inversely related to activity and transcription levels of GSK-3 during embryogenesis. Lastly, after GSK-3 knockdown, we observed changes in the expression of the Wingless (Wnt) downstream target β-catenin as well as in members of other pathways such as the receptor Notch. Taken together, our results show that GSK-3 regulation is essential for R. prolixus oogenesis and embryogenesis.

A global phosphoproteomics analysis of adult Fasciola gigantica by LC–MS/MS

“…Glycogen synthase was phosphorylated by a conserved glycogen synthase kinase 3 (GSK3) in eukaryotes, and GSK3 acted as a downstream component of the Wnt pathway during embryogenesis (Vital et al 2010 ). A study demonstrated that GSK3 was involved in regulation of oogenesis and embryogenesis of Rhodnius prolixus (a blood-feeding insect as a media of Trypanosoma ), and the activity and transcription levels of GSK3 were related to glycogen content (Mury et al 2016 ). In Schistosoma japonicum , GSK3β (one GSK3 isoform) was highly expressed in the eggs (Liu et al 2020a ).…”

Adaptations in energy metabolism and gene family expansions revealed by comparative transcriptomics of three Chagas disease triatomine vectors

“…In Drosophila, adaptive mutations in the Pgm1 locus show latitudinal clinal variation correlating with increased glycogen storage in temperate regions [ 67 , 68 ]. Glycogen storage increases after blood meal in R. prolixus , is required for oogenesis and is completely depleted after prolonged starvation periods [ 69 – 72 ] (Fig. 6 ).…”

A Rhodnius prolixus Insulin Receptor and Its Conserved Intracellular Signaling Pathway and Regulation of Metabolism

“…Although GSKβ3 is a substrate for Akt and therefore has its activity modulated by this kinase, it has been shown that PKA (protein kinase A) and other kinases in the Wnt pathway can also phosphorylate and inactivate this enzyme (91, 92). GSKβ3 was proven to be essential for glycogen metabolism but not lipogenesis during oogenesis and embryogenesis in R. prolixus , in response to both insulin and Wnt receptors (93). Also, triatomine insects, such as R. prolixus , mainly rely on lipids as their motor energy supply, having a remarkably low concentration of sugars in the hemolymph when compared to other insects (94).…”