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3. Summary

The subunits forming the nAChRs constitute a multigene family. In the molecular studies of the subunits as well as in the functional studies of the receptors, the constant consideration of this fact allows a better understanding of the observed phenomenons. I tried to reconstruct the integrity of this family concept.

My phD work can be arranged according two major pathways, developed in parallel.

On one hand, I analyzed the sequence of nicotinic receptors subunits. I studied the phylogenetic relationships between subunit coding genes, using their sequences but also their structure. During this work I developed a database on internet, which contains the sequences of the ligand-gated ion channel subunits. The subunit subfamilies defined according to the phylogenetic reconstruction are congruent with the receptor groups formed from functional criteria (anatomical, biochemical and pharmacological). Then, I performed a prediction of the secondary structure of a typical nAChR subunit. I used for that the 3rd generation algorithms. I incorporated other data into this prediction, either predicted (topology, solvant accessibility) or experimentally determined (binding site, MIR), in order to draw a 2D representation of the prototypic subunit.

On the other hand, I examined the relations between the distributions of the different neuronal subunits in the rodent brain. I observed this distribution in the embryonic and adult rat and also in transgenic mice lacking particular nAChR subunit. This work allowed to map the expression of the $\alpha $6 subunit, which was still unknown. I found that this subunit is highly expressed in the catecholaminergic cells of the brain, which indicate a putative role in the nicotinic transmission at these anatomical levels. In order to further explore the roles of $\alpha $6, I blocked its expression in vivo with antisense oligonucleotides. This experiment reveals that an involvement of the $\alpha $6 subunit in the nicotine-induced locomotor activity.


next up previous contents
Next: 4. Publications principales Up: No Title Previous: 2. Résumé
Nicolas Le Novère
1999-06-19