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  Director : Jean-Pierre CHANGEUX (changeux@pasteur.fr)


  abstract

 

During the year 2001, the Unit has achieved : the preparation of the extracellular domain of neuronal nicotinic receptor alpha 7 in soluble form ; the identification of N-terminal segments conferring desensitization ; the demonstration of the tonic release of acetylcholine ; the demonstration of the diversity of nicotinic receptor subunits in dopaminergic mesencephalic neurons ; the altered behavior and physiology of CGRP knockout mice.



  report

cale

The activity of the " Receptors and Cognition CNRS 2182 " unit is centered on the study of nicotinic acetylcholine receptor, an "allosteric" membrane protein involved in the transduction of chemical neurotransmitter signals into electrical response at the level of the postsynaptic membrane of the neuromuscular junction and of the central nicotinic synapses.

The three main objectives are : (1) identification, at the amino acid level, of the elementary structures engaged in the recognition of nicotinic ligands, in ionic selectivity and transport and their diverse modes of "allosteric" coupling and " up regulation " ; (2) the regulatory mechanisms of gene expression involved in the focal distribution of nicotinic receptors in muscle endplate postsynaptic membrane (in the course of development and in the adult) and (3) the neural processes, in the dendritic vs. axonal compartments of central neurons involved in learning and reward mechanisms associated with nicotine addiction and various brain pathologies.

The methods used to attain the first objective include affinity labeling by specific ligands under rapid mixing conditions, peptide microsequencing, site-directed mutagenesis, stopped-flow with fluorescent ligands in wild type and mutant brain nicotinic receptors, crystallization of the purified protein (or specific fragments) and analysis of the three-dimensional structure. To attain objectives 2 and 3, the most recent advances in recombinant DNA technologies, cloning and sequencing of cDNAs in situ hybridization, promoter analyses, in vivo and in vitro transfection experiments, cloning of transcription factors and conditional homologous recombination in vivo are being exploited, along with cell biology methods such as confocal microscopy.

Ongoing applications of the current work to medicine include : (1) the pharmacology of peripheral and central nicotinic synapses ; (2) the pathology of innervated skeletal muscle and after denervation, myasthenia gravis ; and (3) brain defects resulting from (or associated with) alterations of nicotinic receptors : epilepsy, Alzheimer's and Parkinson's disease, analgesia, aging and nicotine addiction.

Among the original papers published in 2001, one may quote :

1) The development of a method for soluble overexpression of the alpha 7 nicotinic acetylcholine receptor extracellular domain (Fischer et coll. 2001) (collaboration with A. Bacher) ; 2) the identification of N-terminal segments for the b2 subunit conferring desensitization (Bohler et coll. 2001) ; 3) the evidence for a molecular and cellular diversity of nicotinic receptor subunits in the midbrain dopaminergic nuclei (Klink et coll. 2001) ; 4) the demonstration of a tonic nicotinic modulation of serotominergic transmission in the spinal cord (Cordero-Erausquin and Changeux, 2001) ; 5) the evidence for repressive phenomena in the visual system of b2-subunit knockout mice (Rossi et coll. 2001) (collaboration with L. Maffei) ; 6) the altered neuroadaptation in opiate dependance and neurogenic inflammatory nociception in alphaCGRP mice (Salmon et coll. 2001).



  web site

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  publications

puce Publications of the unit on Pasteur's references database


  personnel

  Office staff Researchers Scientific trainees Other personnel
 

ADJEMIAN, Martine – changeux@pasteur.fr ou jgex @pasteur.fr GEX, Jacqueline – jgex@pasteur.fr ou changeux@pasteur.fr

BOURGEOIS, Jean-Pierre, CNRS, DR2 : jpbourg@pasteur.fr

CORRINGER, Pierre-Jean, CNRS, CR1 : pjcorrin@pasteur.fr

DEVILLERS-THIERY, Anne, Sous-Directeur au Collège de France : devill@pasteur.fr

GRANON, Sylvie, Pasteur, CR2 : granon@pasteur.fr (arrived March 1st 2001)

KERSZBERG, Michel, CNRS, DR2 : mkersz@pasteur.fr

LENA, Clément, INSERM, CR2 (stagiaire) : clena@pasteur.fr (arrived August 16, 2001)

LE NOVÈRE, Nicolas, CNRS, CR2 (stagiaire) : lenov@pasteur.fr (arrived October 1st 2001)

MASKOS, Uwe, Pasteur, CR2 : umaskos@pasteur.fr

NGHIEM, Hoang-Oanh, CNRS, CR1 : honghiem@pasteur.fr

BORDE, Nathalie, ATER Collège de France (left Septembre 2001)

CHAMPTIAUX, Nicolas, French PhD student : champtia@pasteur.fr (ATER Collège de France)

CORDERO-ERAUSQUIN, Matilde, French PhD student: cordero@pasteur.fr (bourse MRT)

GISIGER, Thomas, Canadian Postdoc (left september 2001) (canadian fellowship)

GRAILHE, Régis, French Posdoc : rgrailhe@pasteur.fr (PTR fellowship)

GRUTTER, Thomas, French Postdoc : grutter@pasteur.fr (CEE salary)

HAN, Zhi-Yan, Chinese PhD student: zyhan@pasteur.fr (Sté de Tabacologie fellowship)

LE MAGUERESSE, Corentin, French PhD student:clemag@pasteur.fr (MRT fellowship)

MECHAWAR, Naguib, Canadian postdoc: mechawar@pasteur.fr (arrived December 3rd 2001)

PAAS, Yoav, Maître de conférence associé Collège de France : ypaas@pasteur.fr

ROSSI, Francesco Italian Postdoc : frossi@pasteur.fr (EMBO fellowship)

SALLETTE, Jérôme, French PhD student: sallette@pasteur.fr (CNRS engineer fellowship)

SUNESEN, Morten, Danish Postdoc

MSUNESEN@pasteur.fr (arrived March 1st, 2001) (danish fellowship)

DUFRESNE, Virginie, Engineer, Pasteur (arrived December 3rd 2001)

HUCHET, Monique, Engineer, Collège de France : mohuchet@pasteur.fr

PONS, Engineer, Collège de France : spons@pasteur.fr

SALMON, Anne-Marie, Engineer Pasteur : asalmon@pasteur.fr

STEINMETZE-MEGE, Dominique, Engineer Pasteur, (left September 2001)

LE POUPON, Chantal, Technician Collège de France : cpoupon@pasteur.fr

LE SOURD, Anne-Marie, Technician CNRS : lesourd@pasteur.fr

SOUDANT, Martine, Technician Pasteur


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