Structural insights into PYR/PYL/RCAR ABA receptors and PP2Cs

[EN] Abscisic acid (ABA) plays an essential function in plant physiology since it is required for biotic and abiotic stress responses as well as control of plant growth and development. A new family of soluble ABA receptors, named PYR/PYL/RCAR, has emerged as ABA sensors able to inhibit the activity of specific protein phosphatases type-2C (PP2Cs) in an ABA-dependent manner. The structural and functional mechanism by which ABA is perceived by these receptors and consequently leads to inhibition of the PP2Cs has been recently elucidated. The module PYR/PYL/RCAR-ABA-PP2C offers an elegant and unprecedented mechanism to control phosphorylation signaling cascades in a ligand-dependent manner. The knowledge of their three-dimensional structures paves the way to the design of ABA agonists able to modulate the plant stress response. (C) 2010 Elsevier Ireland Ltd. All rights reserved.We are grateful to the European Synchrotron Radiation Facility (ESRF) and the EMBL for access to macromolecular crystallography beam lines. Work in the laboratory of Dr Rodriguez is supported by grant BIO2008-00221 from Ministerio de Educación y Ciencia and Fondo Europeo de Desarrollo Regional and Consejo Superior de Investigaciones Científicas (fellowships to JS, RA and LR; Juan de la Cierva contract to MGG). Access to the high Throughput Crystallization facility of the Partnership for Structural Biology in Grenoble (PSB) (https://htxlab.embl.fr) was supported by the European Community – Research InfrastructureAction PCUBE under the FP7 “Capacities” specific program.Santiago Cuéllar, J.; Dupeux, F.; Betz, K.; Antoni-Alandes, R.; González Guzmán, M.; Rodriguez, L.; Márquez, JA.... (2012). Structural insights into PYR/PYL/RCAR ABA receptors and PP2Cs. Plant Science. 182:3-11. https://doi.org/10.1016/j.plantsci.2010.11.014S31118

Charakterisierung GABAerger Hemmung im visuellen System von Wildtyp- und genetisch veränderten Mäusen

Die Zielsetzung dieser Arbeit liegt in der Charakterisierung der GABAergen Hemmung in ausgewählten Kerngebieten des visuellen Systems. Dabei wird zunächst anhand von elektrophysiologischen und pharmakologischen Messungen die Existenz des $GABA_{C}$-Rezeptors $(GABA_{C}R)$ in diesen Gehirnstrukturen überprüft und der Anteil dieses Rezeptors an der gesamten Inhibition quantifiziert. Zur Bestimmung inhibitorischer postsynaptischer Ströme werden neben den Wildtyp-Mäusen genetisch veränderte Mäuse verwendet: Bei den $\rho$1-Knockout-Mäusen fehlt die $\rho$1-Untereinheit des $GABA_{C}Rs$, bei den $\it Entla$-Mäusen ist die $\rho$2-Untereinheit dieses Rezeptors überexprimiert. Der Vergleich der postsynaptischen Ströme zwischen den drei Mäusestämmen zeigt Unterschiede in der Kinetik $GABA_{C}R$ vermittelter Ströme auf. Des Weiteren werden sowohl innerhalb als auch zwischen zwei verschiedenen Kerngebieten des visuellen Systems GABAerge Verbindungen untersucht und die Beteiligung des $GABA_{C}Rs$ an diesen Projektionen ermittelt

Plasma Metabolome Signature Indicative of Germline Status Independent of Cancer Incidence.

Individuals carrying a pathogenic germline variant in the breast cancer predisposition gene BRCA1 (gBRCA1+) are prone to developing breast cancer. Apart from its well-known role in DNA repair, BRCA1 has been shown to powerfully impact cellular metabolism. While, in general, metabolic reprogramming was named a hallmark of cancer, disrupted metabolism has also been suggested to drive cancer cell evolution and malignant transformation by critically altering microenvironmental tissue integrity. Systemic metabolic effects induced by germline variants in cancer predisposition genes have been demonstrated before. Whether or not systemic metabolic alterations exist in gBRCA1+ individuals independent of cancer incidence has not been investigated yet. We therefore profiled the plasma metabolome of 72 gBRCA1+ women and 72 age-matched female controls, none of whom (carriers and non-carriers) had a prior cancer diagnosis and all of whom were cancer-free during the follow-up period. We detected one single metabolite, pyruvate, and two metabolite ratios involving pyruvate, lactate, and a metabolite of yet unknown structure, significantly altered between the two cohorts. A machine learning signature of metabolite ratios was able to correctly distinguish between gBRCA1+ and controls in ~82%. The results of this study point to innate systemic metabolic differences in gBRCA1+ women independent of cancer incidence and raise the question as to whether or not constitutional alterations in energy metabolism may be involved in the etiology of BRCA1-associated breast cancer