Dataset Information

LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons.

ABSTRACT: The enhanced cognitive abilities characterizing the human species result from specialized features of neurons and circuits. Here, we report that the hominid-specific gene LRRC37B encodes a receptor expressed in human cortical pyramidal neurons (CPNs) and selectively localized to the axon initial segment (AIS), the subcellular compartment triggering action potentials. Ectopic expression of LRRC37B in mouse CPNs in vivo leads to reduced intrinsic excitability, a distinctive feature of some classes of human CPNs. Molecularly, LRRC37B binds to the secreted ligand FGF13A and to the voltage-gated sodium channel (Nav) β-subunit SCN1B. LRRC37B concentrates inhibitory effects of FGF13A on Nav channel function, thereby reducing excitability, specifically at the AIS level. Electrophysiological recordings in adult human cortical slices reveal lower neuronal excitability in human CPNs expressing LRRC37B. LRRC37B thus acts as a species-specific modifier of human neuron excitability, linking human genome and cell evolution, with important implications for human brain function and diseases.

SUBMITTER: Libe-Philippot B

PROVIDER: S-EPMC10754148 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons.

Libé-Philippot Baptiste B Lejeune Amélie A Wierda Keimpe K Louros Nikolaos N Erkol Emir E Vlaeminck Ine I Beckers Sofie S Gaspariunaite Vaiva V Bilheu Angéline A Konstantoulea Katerina K Nyitrai Hajnalka H De Vleeschouwer Matthias M Vennekens Kristel M KM Vidal Niels N Bird Thomas W TW Soto Daniela C DC Jaspers Tom T Dewilde Maarten M Dennis Megan Y MY Rousseau Frederic F Comoletti Davide D Schymkowitz Joost J Theys Tom T de Wit Joris J Vanderhaeghen Pierre P

Cell 20231201 26

The enhanced cognitive abilities characterizing the human species result from specialized features of neurons and circuits. Here, we report that the hominid-specific gene LRRC37B encodes a receptor expressed in human cortical pyramidal neurons (CPNs) and selectively localized to the axon initial segment (AIS), the subcellular compartment triggering action potentials. Ectopic expression of LRRC37B in mouse CPNs in vivo leads to reduced intrinsic excitability, a distinctive feature of some classes ...[more]

PMID: 38134874

Similar Datasets

Project description:The sensitivity of neurons from the honey bee olfactory system to pyrethroid insecticides was studied using the patch-clamp technique on central 'antennal lobe neurons' (ALNs) in cell culture. In these neurons, the voltage-dependent sodium currents are characterized by negative potential for activation, fast kinetics of activation and inactivation, and the presence of cumulative inactivation during train of depolarizations. Perfusion of pyrethroids on these ALN neurons submitted to repetitive stimulations induced (1) an acceleration of cumulative inactivation, and (2) a marked slowing of the tail current recorded upon repolarization. Cypermethrin and permethrin accelerated cumulative inactivation of the sodium current peak in a similar manner and tetramethrin was even more effective. The slow-down of channel deactivation was markedly dependent on the type of pyrethroid. With cypermethrin, a progressive increase of the tail current amplitude along with successive stimulations reveals a traditionally described use-dependent recruitment of modified sodium channels. However, an unexpected decrease in this tail current was revealed with tetramethrin. If one considers the calculated percentage of modified channels as an index of pyrethroids effects, ALNs are significantly more susceptible to tetramethrin than to permethrin or cypermethrin for a single depolarization, but this difference attenuates with repetitive activity. Further comparison with peripheral neurons from antennae suggest that these modifications are neuron type specific. Modeling the sodium channel as a multi-state channel with fast and slow inactivation allows to underline the effects of pyrethroids on a set of rate constants connecting open and inactivated conformations, and give some insights to their specificity. Altogether, our results revealed a differential sensitivity of central olfactory neurons to pyrethroids that emphasize the ability for these compounds to impair detection and processing of information at several levels of the bees olfactory pathway.

Dataset Information

LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons.

Publications

LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets