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The Journal of Neuroscience, April 13, 2005, 25(15):3793-3800; doi:10.1523/JNEUROSCI.4595-04.2005

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Cellular/Molecular
Ric-8B, an Olfactory Putative GTP Exchange Factor, Amplifies Signal Transduction through the Olfactory-Specific G-Protein Golf

Luiz Eduardo C. Von Dannecker, ^* Adriana F. Mercadante, ^* and Bettina Malnic

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil

The olfactory system is able to detect a large number of chemical structures with a remarkable sensitivity and specificity. Odorants are first detected by odorant receptors present in the cilia of olfactory neurons. The activated receptors couple to an olfactory-specific G-protein (Golf), which activates adenylyl cyclase III to produce cAMP. Increased cAMP levels activate cyclic nucleotide-gated channels, causing cell membrane depolarization. Here we used yeast two-hybrid to search for potential regulators for Golf. We found that Ric-8B (for resistant to inhibitors of cholinesterase), a putative GTP exchange factor, is able to interact with Golf. Like Golf, Ric-8B is predominantly expressed in the mature olfactory sensory neurons and also in a few regions in the brain. The highly restricted and colocalized expression patterns of Ric-8B and Golf strongly indicate that Ric-8B is a functional partner for Golf. Finally, we show that Ric-8B is able to potentiate Golf-dependent cAMP accumulation in human embryonic kidney 293 cells and therefore may be an important component for odorant signal transduction.

Key words: olfactory neurons; signal transduction; GEF; G-protein; G-protein-coupled receptors; odorant receptors; synembryn

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Received Nov 9, 2004; revised February 5, 2005; accepted March 7, 2005.

This article has been cited by other articles:

				B. Malnic and D.S. Kerr Using GEFs to Deorphanize Odorant Receptors Chem Senses, September 26, 2008; (2008) bjn058v1. [Full Text] [PDF]

				S. J. Kleene The Electrochemical Basis of Odor Transduction in Vertebrate Olfactory Cilia Chem Senses, August 14, 2008; (2008) bjn048v1. [Abstract] [Full Text] [PDF]

				K. Yoshikawa and K. Touhara Myr-Ric-8A Enhances G{alpha}15-Mediated Ca2+ Response of Vertebrate Olfactory Receptors Chem Senses, August 5, 2008; (2008) bjn047v1. [Abstract] [Full Text] [PDF]

				D. P. McEwen, R. K. Koenekoop, H. Khanna, P. M. Jenkins, I. Lopez, A. Swaroop, and J. R. Martens Hypomorphic CEP290/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons PNAS, October 2, 2007; 104(40): 15917 - 15922. [Abstract] [Full Text] [PDF]

				H. Zhuang and H. Matsunami Synergism of Accessory Factors in Functional Expression of Mammalian Odorant Receptors J. Biol. Chem., May 18, 2007; 282(20): 15284 - 15293. [Abstract] [Full Text] [PDF]

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				G. G. Tall and A. G. Gilman Resistance to inhibitors of cholinesterase 8A catalyzes release of G{alpha}i-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/G{alpha}i-GDP complexes PNAS, November 15, 2005; 102(46): 16584 - 16589. [Abstract] [Full Text] [PDF]

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