Biology subjects

Martinvalet, D.

Publications and source records attributed to Martinvalet, D..

2 recordsLinked to original sources

bioRxiv2022

Apical-to-basal graded ROS metabolism in intact Hydra leads to distinct levels of injury-induced ROS signaling in apical and basal regenerating tips

After mid-gastric bisection, Hydra regenerates a head from the lower half and a basal disc from the upper one. What signals elicit two distinct regenerative responses in bisected Hydra remains unknown. A mathematical modeling approach based on quantitative data linked to MAPK activation and injury-induced cell death predicts an immediate release of a locally restricted short-lived signal in apical-regenerating tips. We found that Reactive oxygen species (ROS) fulfill this role as evidenced by the injury-induced production of hydrogen peroxide (H2O2), three-fold higher in apical-regenerating tips than in basal ones. By contrast, mitochondrial superoxide (mtO2.-) is similarly produced on each side of the cut, playing a positive role on wound healing as mtO2.- scavenging delays healing whereas knocking-down Super Oxide Dismutase (SOD) leads to mtO2.- accumulation and acceleration of wound-healing. In intact Hydra, the ROS-processing enzyme activities are inversely graded along the body column, basal-to-apical for SOD and apical-to-basal for catalase, explaining the asymmetrical levels of H2O2 after bisection. High H2O2 levels trigger injury-induced cell death via paracrine signaling in apical-regenerating tips, where NOX4 and CYBB enzymes amplify them. Hence, the asymmetrical regulation of H2O2 levels immediately after amputation is crucial to activate two distinct regenerative responses in Hydra.

developmental biology↗

bioRxiv2020

Cdk5 and GSK3β inhibit Fast Endophilin-Mediated Endocytosis

Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Parallel to Clathrin-mediated endocytosis, additional Clathrin-independent endocytic routes exist, including fast Endophilin-mediated endocytosis (FEME). The latter is not constitutively active but requires the activation of selected receptors. In cell culture, however, the high levels of growth factors in the regular culture media induce spontaneous FEME, which can be suppressed upon serum starvation. Thus, we predicted a role for protein kinases in this growth factor receptor-mediated regulation of the pathway. Using chemical and genetic inhibition, we found that Cdk5 and GSK3{beta} are negative regulators of FEME. Their inhibition was sufficient to activate FEME promptly in resting cells and boosted the production of endocytic carriers containing {beta} 1-adrenergic receptor, following dobutamine addition. We established that the kinases suppress FEME at several levels. They control Dynamin-1 and Dynein recruitment and sorting of cargo receptors such as Plexin A1 and ROBO1 into FEME carriers. They do so by antagonizing the binding of Endophilin to Dynamin-1 as well as to Collapsin response mediator protein 4 (CRMP4), a Plexin A1 adaptor. Cdk5 and GSK3{beta} also hamper the binding and recruitment of Dynein onto FEME carriers by Bin1. Interestingly, we found that GSK3{beta} binds to Endophilin, thus imposing a local regulation of FEME. Collectively, these findings place the two kinases as key regulators of FEME, licensing cells for rapid uptake by the pathway only upon when Cdk5 and GSK3{beta} activity is low.

cell biology↗