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Bayındır Group Journal Club The Sense of Smell and Its Cellular and Molecular Logic Ekin Özgür 16/12/2009 Fortune Telling by René Magritte “This is not a nose” INTRODUCTION • The sense of smell remained the most enigmatic of our senses until recently • Our lives are apparently dominated by the visual sense, but often smells trigger much deeper emotional responses • All living organisms can detect and identify chemical substances in their environment • Humans can recognise more than 10.000 different scents, while dogs recognise more than 200.000 • Detection limit: 4 x 10-15 g/l Pioneering Work Hypotheses: • The odorant receptors are likely to belong to the superfamily of receptor proteins that transduce intracellular signals by coupling to GTP-binding proteins • odorant receptors themselves should exhibit significant diversity and are therefore likely to be encoded by a multigene family • expression of the odorant receptors should be restricted to the olfactory epithelium Olfactory Epithelium Cellular Mechanism Results Olfactory Receptor Genes • 400 functional genes in humans (Three genes in retina) • 1200 functional genes in mice • 3-5 % of mammalian genome: The largest gene family Conbinational Receptor Code • 10.000 scents with 400 receptors: HOW? One Neuron-One Receptor • In mammals with 1000 receptor, each receptor is expressed in 0.1 % of neurons • In fish with 100 distinct receptors, each receptor is expressed in 1 % of neurons • Each neuron expresses only one type of receptor Arranging Neurons and Axons in the Brain Arranging Neurons and Axons in the Brain Summary Questions to Be Answered • How only one olfacrory receptor gene is expressed in one neuron, what is the mechanism? How a particular gene is selected? • Neurons generally do not reproduce, however olfactory neurons have lives of 70-90 days. They are replaced by stem cells. How is the numbers of each type of neuron balanced? • How do the olfactory neurons connect to the correct glomerulus? • How do the olfactory receptors recognize the specific smell patterns? Is the recognition is related to the shape of the molecule, or is it related to quantum mechanical effects such as electron tunneling?