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Chevrier, N.

Publications and source records attributed to Chevrier, N..

3 recordsLinked to original sources

βII and βIII spectrin paralogues define robustness and specialization of the neuronal membrane periodic skeleton

Neuron connectivity and signal processing rely on a complex, dynamic morphology regulated by the cytoskeleton. The membrane-associated periodic skeleton (MPS), a 190-nm periodic actin-spectrin lattice, is a conserved feature of neurons. Here, we show that the dendritic MPS is built from a dual {beta}-spectrin system in which {beta}II- and {beta}III-spectrins are co-expressed and interleaved at the nanoscale in shafts and spine necks. 3D MINFLUX nanoscopy suggests that these paralogues form both homotypic ({beta}II- or {beta}III-only) and heterotypic ({beta}II/{beta}III) tetramers with an approximately 100-nm radial periodicity. Either paralogue alone is sufficient to maintain lattice architecture, whereas their combined loss disrupts MPS integrity. Using targeted mutagenesis, we show that actin binding is required to stabilize both paralogues within the MPS, whereas {beta}III-spectrin additionally depends on phosphoinositide interactions. Our findings reveal that, unlike the axonal MPS, the dendritic MPS is a composite scaffold in which structural redundancy coexists with paralogue-specific regulatory mechanisms, with potential consequences for synaptic function.

neuroscience↗

Organism-Wide Analysis of Sepsis Reveals Mechanisms of Systemic Inflammation

Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the impact of sepsis across organs of the body is rudimentary. Here, using mouse models of sepsis, we generate a dynamic, organism-wide map of the pathogenesis of the disease, revealing the spatiotemporal patterns of the effects of sepsis across tissues. These data revealed two interorgan mechanisms key in sepsis. First, we discover a simplifying principle in the systemic behavior of the cytokine network during sepsis, whereby a hierarchical cytokine circuit arising from the pairwise effects of TNF plus IL-18, IFN-{gamma}, or IL-1{beta} explains half of all the cellular effects of sepsis on 195 cell types across 9 organs. Second, we find that the secreted phospholipase PLA2G5 mediates hemolysis in blood, contributing to organ failure during sepsis. These results provide fundamental insights to help build a unifying mechanistic framework for the pathophysiological effects of sepsis on the body.

immunology↗

Bioorthogonal labeling of transmembrane proteins with non-canonical amino acids allows access to masked epitopes in live neurons

Progress in biological imaging is intrinsically linked to advances in labeling methods. The explosion in the development of high-resolution and super-resolution imaging calls for new approaches to label targets with small probes. These should allow to faithfully report the localization of the target within the imaging resolution - typically nowadays a few nanometers - and allow access to any epitope of the target, in the native cellular and tissue environment. We report here the development of a complete labeling and imaging pipeline using genetic code expansion and non-canonical amino acids in primary neurons that allows to fluorescently label masked epitopes in target transmembrane proteins in live neurons, both in dissociated culture and organotypic brain slices. This allowed us to image the differential localization of two glutamate receptor auxiliary proteins in complex with their partner with a variety of methods including widefield, confocal, and dSTORM super-resolution microscopy.

cell biology↗