New Modes of GPCR Signalling
New Modes of GPCR Signalling
New Modes of GPCR Signalling
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Effects <strong>of</strong> Cyclic Nucleotide Gated Channel Knockout on the Olfactory<br />
Bulb Analyzed by Quantitative Phospho-Proteomics<br />
Fei Liu 1 , Xiao-Ping Rao, Lei-Ke Zhang 2 , Lin Guo 2 , Fuqiang Xu 1<br />
1State Key Laboratory <strong>of</strong> Magnetic Resonance and Atomic and Molecular<br />
Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute <strong>of</strong> Physics<br />
and Mathematics Chinese Academy <strong>of</strong> Sciences, Wuhan 430071, P. R. China<br />
2College <strong>of</strong> Life Sciences, Wuhan University, Wuhan 430072, P. R. China<br />
When odorant molecules enter nasal cavity and are dissolved in the mucus covering the<br />
olfactory epithelium, they bind with odorant receptor proteins in the cilia <strong>of</strong> the<br />
olfactory sensory neurons, leading to a series <strong>of</strong> signal transduction processes:<br />
activation <strong>of</strong> trimeric G-proteins and then nucleotide cyclase, to increase cAMP<br />
concentration, opening <strong>of</strong> cyclic nucleotide gated (CNG) channel, and at last, generating<br />
action potentials that are sent to the olfactory bulb. CNG channel, mainly expressed in<br />
visual and olfactory systems, is non-selective to cations. It is necessary to lead to<br />
depolarization <strong>of</strong> the olfactory sensory neurons. Knockout <strong>of</strong> one <strong>of</strong> its subunit, cnga2,<br />
give rise to anosmic mice. The transgenic animals have much lower surviving rate,<br />
thinner olfactory epithelium, smaller olfactory bylb and less aggressive behavior. To<br />
investigate the effects <strong>of</strong> long term absence <strong>of</strong> peripheral stimulation on the olfactory<br />
bulb, we used quantitative phosphor-proteomics to analyze the change <strong>of</strong> protein<br />
phosphorylation. We found hundreds <strong>of</strong> phosphorylated proteins and even more<br />
phosphorylated sites. Generally, proteins with significant changes in phosphorylation<br />
are these related to signal transduction, neuronal transmission, homeostasis and<br />
neurogenesis. For examples, GAD1, a GABA synthase, is decrease to 19%; CAMK2b, a<br />
kinase, to 33%; and Slc4a4, a electrogenic sodium bicarbonate cotransporter, to 17%<br />
<strong>of</strong> the control, while Hsp90aa1, heat shock protein HSP 90-alpha, increased by a<br />
101%; and Alpl, a tissue-nonspecific alkaline phosphatase by 346%. The exact roles <strong>of</strong><br />
these proteins in the olfactory bulb are under investigation.<br />
Key words: olfactory bulbs, transgenic mice, phosphoproteins, IMAC/LC-MS
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