Biology subjects

Jaudon, F.

Publications and source records attributed to Jaudon, F..

3 recordsLinked to original sources

bioRxiv2022

The tetraspanin TSPAN5 regulates AMPARs exocytosis by interacting with the AP-4 complex

Intracellular trafficking of AMPA receptors is a tightly regulated process which involves several adaptor proteins, and is crucial for the activity of excitatory synapses in both basal conditions and during synaptic plasticity. We found that, in rat hippocampal neurons, an intracellular pool of the tetraspanin TSPAN5 specifically promotes exocytosis of newly synthesised GluA2-containing AMPA receptors without affecting their internalisation. TSPAN5 mediates this function by interacting with AP-4 and Stargazin and possibly using recycling endosomes as a delivery route. This work highlights TSPAN5 as a new adaptor regulating AMPA receptor trafficking. In addition, it provides a possible mechanism for the intellectual disability symptoms that occur in AP-4 deficiency syndrome.

neuroscience↗

bioRxiv2021

A developmental stage- and Kidins220/ARMS-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

Astroglial cells are key to maintain nervous system homeostasis, as they are able to perceive a wide variety of extracellular signals and to transduce them into responses that may be protective or disruptive toward neighboring neurons through the activation of distinct signaling pathways. Neurotrophins are a family of growth factors known for their pleiotropic effects on neuronal survival, maturation and plasticity. In this work, we investigated: (i) the signaling competence of embryonic and postnatal primary cortical astrocytes exposed to brain-derived neurotrophic factor (BDNF); and (ii) the role of the scaffold protein Kinase D interacting substrate/ankyrin repeat-rich membrane spanning (Kidins220/ARMS), a transmembrane protein that mediates neurotrophin signaling in neurons, in the astrocyte response to BDNF. We found a shift from a kinase-based response in embryonic cells to a predominantly [Ca2+]i-based response in postnatal cultures associated with the decreased expression of the full-length BDNF receptor TrkB. We also found that Kidins220/ARMS contributes to the BDNF-activated intracellular signaling in astrocytes by potentiating both kinase and [Ca2+]i pathways. Finally, Kidins220/ARMS contributes to astrocytes homeostatic function by controlling the expression of the inwardly rectifying potassium channel (Kir) 4.1. Overall, our data contribute to the understanding of the complex role played by astrocytes within the central nervous system and identify Kidins220/ARMS as a novel actor in the increasing number of pathologies characterized by astrocytes dysfunctions.

neuroscience↗

bioRxiv2019

Correction of β3 integrin haplo-insufficiency by CRISPRa normalizes cortical network activity

The extracellular matrix (ECM) plays an essential role in regulating the function of neuronal networks. In many cell types, the ECM exerts its effects through the transmembrane receptors integrins. Here, we investigate whether neuronal integrins regulate network excitability. Specifically, we focus on {beta}3 integrin, which has been associated to autism spectrum disorder and whose expression in neurons is regulated by activity. We have designed CRISPRa tools to titrate {beta}3 integrin expression in neurons. By using multi-electrode arrays and Ca2+imaging, we show that {beta}3 integrin boosts network excitability and synchrony in primary cortical neurons. Crucially, CRISPRa could compensate precisely for {beta}3 integrin haplo-insufficiency, thereby rebalancing level and correlation of neuronal activity. By contrast, rescue strategies based on exogenous gene expression resulted in hyper-active networks firing in unison. Thus, regulation of {beta}3 integrin by CRISPRa provides a precise and efficient system for modulating neuronal network function.

neuroscience↗