Biosciences Research Seminar - The Sodium Leak Channel Nalcn In Physiology And Disease

Part of the Biosciences lunchtime research seminar series

A Biosciences seminar
Date23 September 2021
Time12:30 to 13:30
PlaceEvent held via Microsoft Teams

Speaker: Dr Arnaud Monteil, The Institute of Functional Genomics (IGF) Montpellier. Host: Dr Kyle Wedgwood

Arnaud Monteil obtained his bachelor’s in biological sciences in 1989 in Montpellier (France). He then studied molecular biology and biochemistry at the University of Montpellier from 1989 to 1996. He started his PhD in 1996 under the supervision of Dr Joël Nargeot (University of Montpellier – Montpellier – France) with the objective to clone and characterize T-type voltage-gated calcium channels, a subtype of calcium channels that was not identified at this time. The thesis was successfully defended in 2000 and led to several publications of importance in the fields of ion channels and cellular excitability. After his thesis defense, Arnaud Monteil joined Prof Richard J. Miller’s laboratory as a post-doctoral fellow at the University of Chicago (Chicago – USA) where he identified and cloned a novel type of four-domain ion channel named NALCN. He went back to France in 2001 as a permanent researcher at the National Center for Scientific Research (CNRS). Since then Arnaud Monteil’s research is concerned with ion channels in Dr Philippe Lory’s team (« Ion channels in neuronal excitability and diseases » - Institut de Génomique Fonctionnelle – Montpellier ; http://www.igf.cnrs.fr). Dr Philippe Lory’s team is part of the Laboratory of Excellence « Ion Channel Science and Therapeutics » (http://www.labex-icst.fr/en). The overall ambition of this laboratory of excellence is to become a world-wide recognized cluster in ion channel studies carrying research and innovation at the interface between biology and medicine. In this context, the research projects headed by Arnaud Monteil focus on the study of ion channels’ mutations involved in complex neurological disorders using molecular and electrophysiological techniques both in vitro (cell lines ; primary cultures) and in vivo (animal models). A special emphasis is to search for new molecules modulating ion channels activity that could be relevant to treat human diseases. Of note, Arnaud Monteil supervised 2-year exchange programs (Hubert-Curien Program 2013-2014 and 2020-2021) with Dr Narawut Pakaprot at Mahidol University (Thailand). In addition to his research activity, Arnaud Monteil is the head of a facility to produce viral vectors for research since 2008 (http://www.biocampus.cnrs.fr), is the president of the « Ion Channel » society since 2014 (http://www.canaux-ioniques.fr/) and leads the scientific committee of the Libellas foundation since 2020 (https://fundacionlibellas.org/). Arnaud Monteil is also an elected member of the National Committee of the CNRS (CoNRS, Sub-committee #24 “Aging, Tumorigenesis, Physiology”) since 2016.

 


Abstract

The leak sodium channel NALCN, an atypical member of the four-domain ion channel family, plays a crucial role in the maintenance of the resting membrane potential of several cell types including neurons. Although this ion channel was first identified in 1999, the first functional data were only reported in 2007. Since then, several studies reported a role in pacemaking activity of different types of excitable cells including neurons, myometrial smooth muscle cells and interstitial cells of Cajal. Studies of animal models indicated a large panel of NALCN-related phenotypes including an altered locomotor behaviour and anaesthetic sensitivity, a disruption of respiratory and circadian rythms as well as a neonatal lethality when nalcn is knocked out in mouse. NALCN mutations lead to complex neurodevelopmental syndromes, including infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) and congenital contractures of limbs and face, hypotonia and developmental delay (CLIFAHDD), which are recessively and dominantly inherited, respectively. In my presentation, I will show that NALCN is also a critical player of anterior pituitary cell excitability and how pathogenic variants alter biophysical properties of the NALCN current. In addition, I will present data showing that NALCN does not always conduct a sodium leak current in some cell types.

Attachments
Seminar_Series_Poster_23092021.pdf (475K)

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