Molecular components of signal amplification in olfactory sensory cilia
- PMID: 20231443
- PMCID: PMC2851919
- DOI: 10.1073/pnas.0909032107
Molecular components of signal amplification in olfactory sensory cilia
Abstract
The mammalian olfactory system detects an unlimited variety of odorants with a limited set of odorant receptors. To cope with the complexity of the odor world, each odorant receptor must detect many different odorants. The demand for low odor selectivity creates problems for the transduction process: the initial transduction step, the synthesis of the second messenger cAMP, operates with low efficiency, mainly because odorants bind only briefly to their receptors. Sensory cilia of olfactory receptor neurons have developed an unusual solution to this problem. They accumulate chloride ions at rest and discharge a chloride current upon odor detection. This chloride current amplifies the receptor potential and promotes electrical excitation. We have studied this amplification process by examining identity, subcellular localization, and regulation of its molecular components. We found that the Na(+)/K(+)/2Cl(-) cotransporter NKCC1 is expressed in the ciliary membrane, where it mediates chloride accumulation into the ciliary lumen. Gene silencing experiments revealed that the activity of this transporter depends on the kinases SPAK and OSR1, which are enriched in the cilia together with their own activating kinases, WNK1 and WNK4. A second Cl(-) transporter, the Cl(-)/HCO(3)(-) exchanger SLC4A1, is expressed in the cilia and may support Cl(-) accumulation. The calcium-dependent chloride channel TMEM16B (ANO2) provides a ciliary pathway for the excitatory chloride current. These findings describe a specific set of ciliary proteins involved in anion-based signal amplification. They provide a molecular concept for the unique strategy that allows olfactory sensory neurons to operate as efficient transducers of weak sensory stimuli.
Conflict of interest statement
The authors declare no conflict of interest.
Figures







Similar articles
-
Chloride accumulation in mammalian olfactory sensory neurons.J Neurosci. 2004 Sep 8;24(36):7931-8. doi: 10.1523/JNEUROSCI.2115-04.2004. J Neurosci. 2004. PMID: 15356206 Free PMC article.
-
SPAK/OSR1 regulate NKCC1 and WNK activity: analysis of WNK isoform interactions and activation by T-loop trans-autophosphorylation.Biochem J. 2012 Jan 1;441(1):325-37. doi: 10.1042/BJ20111879. Biochem J. 2012. PMID: 22032326 Free PMC article.
-
Interactions with WNK (with no lysine) family members regulate oxidative stress response 1 and ion co-transporter activity.J Biol Chem. 2012 Nov 2;287(45):37868-79. doi: 10.1074/jbc.M112.398750. Epub 2012 Sep 18. J Biol Chem. 2012. PMID: 22989884 Free PMC article.
-
Cotransporters, WNKs and hypertension: an update.Curr Opin Nephrol Hypertens. 2008 Mar;17(2):186-92. doi: 10.1097/MNH.0b013e3282f5244e. Curr Opin Nephrol Hypertens. 2008. PMID: 18277153 Review.
-
Phosphoregulation of the Na-K-2Cl and K-Cl cotransporters by the WNK kinases.Biochim Biophys Acta. 2010 Dec;1802(12):1150-8. doi: 10.1016/j.bbadis.2010.07.009. Epub 2010 Jul 15. Biochim Biophys Acta. 2010. PMID: 20637866 Free PMC article. Review.
Cited by
-
A comprehensive strategy to identify stoichiometric membrane protein interactomes.Cell Logist. 2012 Oct 1;2(4):189-196. doi: 10.4161/cl.22717. Cell Logist. 2012. PMID: 23676845 Free PMC article.
-
Anoctamin 1 mediates thermal pain as a heat sensor.Curr Neuropharmacol. 2013 Dec;11(6):641-51. doi: 10.2174/1570159X113119990038. Curr Neuropharmacol. 2013. PMID: 24396339 Free PMC article.
-
Intracellular Cl- Regulation of Ciliary Beating in Ciliated Human Nasal Epithelial Cells: Frequency and Distance of Ciliary Beating Observed by High-Speed Video Microscopy.Int J Mol Sci. 2020 Jun 5;21(11):4052. doi: 10.3390/ijms21114052. Int J Mol Sci. 2020. PMID: 32517062 Free PMC article. Review.
-
Anoctamins.Pflugers Arch. 2011 Aug;462(2):195-208. doi: 10.1007/s00424-011-0975-9. Epub 2011 May 21. Pflugers Arch. 2011. PMID: 21607626 Review.
-
Expression of calcium-activated chloride channels Ano1 and Ano2 in mouse taste cells.Pflugers Arch. 2016 Feb;468(2):305-19. doi: 10.1007/s00424-015-1751-z. Epub 2015 Nov 3. Pflugers Arch. 2016. PMID: 26530828
References
-
- Kleene SJ. The electrochemical basis of odor transduction in vertebrate olfactory cilia. Chem Senses. 2008;33:839–859. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous