tailieunhanh - Báo cáo khoa học: Olfactory receptor signaling is regulated by the post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) scaffold multi-PDZ domain protein 1

The unique ability of mammals to detect and discriminate between thou-sands of different odorant molecules is governed by the diverse array of olfactory receptors expressed by olfactory sensory neurons in the nasal epithelium. Olfactory receptors consist of seven transmembrane domain G protein-coupled receptors and comprise the largest gene superfamily in the mammalian genome. | Olfactory receptor signaling is regulated by the post-synaptic density 95 Drosophila discs large zona-occludens 1 PDZ scaffold multi-PDZ domain protein 1 Ruth Dooley1 2 Sabrina Baumgart2 z Sebastian Rasche1 Hanns Hatt1 and Eva M. Neuhaus3 1 Molecular Medicine Lab RCSI Education Research Centre Smurfit Building Beaumont Hospital Dublin Republic of Ireland 2 Department of CellPhysiology Ruhr University Bochum Germany 3 NeuroScience Research Center Charite Universitatsmedizin Berlin Germany Keywords MUPP1 olfactory neuron olfactory receptor PDZ protein signal transduction Correspondence E. M. Neuhaus NeuroScience Research Center Charite Universitatsmedizin Berlin 10117 Berlin Germany Fax 49 30 450 539 970 Tel 49 30 450 539 702 E-mail These authors contributed equally to this work Received 9 September 2009 revised 6 October 2009 accepted 12 October 2009 doi The unique ability of mammals to detect and discriminate between thousands of different odorant molecules is governed by the diverse array of olfactory receptors expressed by olfactory sensory neurons in the nasal epithelium. Olfactory receptors consist of seven transmembrane domain G protein-coupled receptors and comprise the largest gene superfamily in the mammalian genome. We found that approximately 30 of olfactory receptors possess a classical post-synaptic density 95 Drosophila discs large zona-occludens 1 PDZ domain binding motif in their C-termini. PDZ domains have been established as sites for protein-protein interaction and play a central role in organizing diverse cell signaling assemblies. In the present study we show that multi-PDZ domain protein 1 MUPP1 is expressed in the apical compartment of olfactory sensory neurons. Furthermore on heterologous co-expression with olfactory sensory neurons MUPP1 was shown to translocate to the plasma membrane. We found direct interaction of PDZ domains 1 2 of MUPP1 with the C-terminus of olfactory receptors in