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Neurosciences

As Old as Nicotine Dependence

Nicotine receptors are present in very ancient forms of bacteria. This is the surprising discovery1 made by the team directed by Pierre-Jean Corringer, a neuroscientist at the Institut Pasteur,2 who has recently identified a distant ancestor of this type of protein. “For many years, we thought that nicotine receptors were only found in specific brain cells of the most evolved species. We have now discovered that these receptors have an ancestor in primitive cyanobacteria,3” states Corringer. From the known genomic sequences of different bacteria, his team has, for the first time, been able to isolate proteins homologous with nicotine receptors, the receptors responsible for tobacco addiction in the brain. These proteins have even been found in Gloeobacter violaceus, a rudimentary cyanobacterium which lived on our planet well before the first animal species appeared. This unexpected discovery demonstrates the existence of a bacterial ancestor for nicotine receptors. They initially appeared in a very simple form, but their complexity gradually increased during cerebral evolution, in parallel to increased neuronal communications. Scientists know that nicotine receptors are five domain proteins folded in a pentagonal structure around a central ion channel that crosses the cell membrane. This “tunnel”–the keystone of intercellular communication–allows specific ions to enter and exit the cell. “When you smoke, nicotine rapidly reaches the brain. It binds to specific receptors, causing their ion channel to open, and then excites the neurons which belong to the circuits associated with reward,” explains Corringer. “The fact that the bacterial protein has a remarkably simplified structure provides a unique opportunity to decipher its structure/function relationship. It also makes it easier to crystallize the protein in order to analyze its three-dimensional structure at an atomic scale.” Understanding the structure of an ancestor will, by “homology,” generate knowledge of the functioning of our own receptors and their evolution. “If we clearly understand the structure and function of these receptors, we should be able to develop new treatments to fight tobacco addiction.”

 

Alissar Cheaïb

Notes :

1. N. Bocquet et al., “A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family 2,” Nature. 445: 116-119. 2007.
2. Laboratoire Récepteurs et cognition (CNRS / Institut Pasteur).
3. Cyanobacteria are a sub-class of bacteria, previously called blue-green algae. They appeared about 3.8 billion years ago and may have been at the origin of the development of animal life on Earth due to their production of oxygen by photosynthesis.


Contacts :

Pierre-Jean Corringer
Laboratoire Récepteurs et cognition, Paris.
pjcorrin@pasteur.fr


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