GABAA receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl--sensitive WNK1 kinase

This is the final version of the article. Available from the publisher via the DOI in this record.There is another ORE record for this publication: http://hdl.handle.net/10871/33406The K+-Cl-co-transporter KCC2 (SLC12A5) tunes the efficacy of GABAAreceptor-mediated transmission by regulating the intraneuronal chloride concentration [Cl-]i. KCC2 undergoes activity-dependent regulation in both physiological and pathological conditions. The regulation of KCC2 by synaptic excitation is well documented; however, whether the transporter is regulated by synaptic inhibition is unknown. Here we report a mechanism of KCC2 regulation by GABAAreceptor (GABAAR)-mediated transmission in mature hippocampal neurons. Enhancing GABAAR-mediated inhibition confines KCC2 to the plasma membrane, while antagonizing inhibition reduces KCC2 surface expression by increasing the lateral diffusion and endocytosis of the transporter. This mechanism utilizes Cl-as an intracellular secondary messenger and is dependent on phosphorylation of KCC2 at threonines 906 and 1007 by the Cl--sensing kinase WNK1. We propose this mechanism contributes to the homeostasis of synaptic inhibition by rapidly adjusting neuronal [Cl-]ito GABAAR activity.This work was supported in part by Inserm, Sorbonne Université-UPMC, as well as the Fondation pour la Recherche Médicale (Equipe FRM DEQ20140329539 to J.C.P.), the Human Frontier Science Program (RGP0022/2013 to J.C.P.) and the Fondation pour la Recherche sur le Cerveau (to S.L.). Equipment at the IFM was also supported by DIM NeRF from Région Ile-de-France and by the FRC/Rotary ‘Espoir en tête’. M.H. was the recipient of a doctoral fellowship from the Université Pierre and Marie Curie, as well as from Bio-Psy Laboratory of excellence. K.T.K. is supported by the National Institutes of Health, the Simons Foundation, and the March of Dimes Foundation Basil O’Connor Award. The Poncer/Lévi lab is affiliated with the Paris School of Neuroscience (ENP) and the Bio-Psy Laboratory of excellence

Plastome-wide rearrangements and gene losses in carnivorous Droseraceae

The plastid genomes of four related carnivorous plants (Drosera regia, Drosera erythrorhiza, Aldrovanda vesiculosa and Dionaea muscipula) were sequenced to examine changes potentially induced by the transition to carnivory. The plastid genomes of the Droseraceae show multiple rearrangements, gene losses and large expansions or contractions of the inverted repeat. All the ndh genes are lost or non-functional, as well as in some of the species, clpP1, ycf1, ycf2 and some tRNA genes. Uniquely amongst land plants, the trnK gene has no intron. Carnivory in the Droseraceae coincides with changes in plastid gene content similar to those induced by parasitism and mycoheterotrophy, suggesting parallel changes in chloroplast function due to the similar switch from autotrophy to (mixo-) heterotrophy. A molecular phylogeny of the taxa based on all shared plastid genes indicates that the ‘snap-traps’ of Aldrovanda and Dionaea have a common origin

Molecular phylogenetics of Alchemilla, Aphanes and Lachemilla (Rosaceae) inferred from plastid and nuclear intron and spacer DNA sequences, with comments on generic classification

Alchemilla (the lady's mantles) is a well known but inconspicuous group in the Rosaceae, notable for its ornamental leaves and pharmaceutical properties. The systematics of Alchemilla has remained poorly understood, most likely due to confusion resulting from apomixis, polyploidisation and hybridisation, which are frequently observed in the group, and which have led to the description of a large number of (micro-) species. A molecular phylogeny of the genus, including all sections of Alchemilla and Lachemilla as well as five representatives of Aphanes, based on the analysis of the chloroplast trnL-trnF and the nuclear ITS regions is presented here. Gene phylogenies reconstructed from the nuclear and chloroplast sequence data were largely congruent. Limited conflict between the data partitions was observed with respect to a small number of taxa. This is likely to be the result of hybridisation/introgression or incomplete lineage sorting. Four distinct clades were resolved, corresponding to major geographical division and life forms: Eurasian Alchemilla, annual Aphanes, South American Lachemilla and African Alchemilla. We argue for a wider circumscription of the genus Alchemilla, including Lachemilla and Aphanes, based on the morphology and the phylogenetic relationships between the different clades

Ancistrocladus benomensis (Ancistrocladaceae):A new species from Peninsular Malaysia

Ancistrocladus benomensis Rischer & G. Bringmann, a new species from Gunung Benom, Malaysia is described and illustrated. Diagnostic notes concerning morphology, occurrence of specific naphthylisoquinoline alkaloids, and support from molecular analyses are provided

Six naphthylisoquinoline alkaloids and a related benzopyranone from a Congolese Ancistrocladus species related to Ancistrocladus congolensis

From the roots of a recently discovered Ancistrocladus taxon, with close affinities to Ancistrocladus congolensis regarding molecular ITS sequence data, six naphthylisoquinoline alkaloids, 5′-O-demethylhamatine (2), 5′-O-demethylhamatinine (3), 6-O-demethylancistroealaine A (4), 6,5′-O,O-didemethylancistroealaine A (5), 5-epi-6-O-methylancistrobertsonine A (6), and 5-epi-4′-O-demethylancistrobertsonine C (7), have been isolated, along with a likewise benzopyranone carboxylic acid, 8. The structural elucidation succeeded by chemical, spectroscopic, and chiroptical methods. Their bioactivities were tested against protozoan parasites causing severe tropical diseases. Furthermore, eight known related alkaloids were identified