Home LiteratureArticle Details
PMID: 19561302 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 106 ·No. 28 ·2009-07-14 ·Pages 11776-81

Stephan AB, Shum EY, Hirsh S, Cygnar KD, Reisert J, Zhao H

Abstract

For vertebrate olfactory signal transduction, a calcium-activated chloride conductance serves as a major amplification step. However, the molecular identity of the olfactory calcium-activated chloride channel (CaCC) is unknown. Here we report a proteomic screen for cilial membrane proteins of mouse olfactory sensory neurons (OSNs) that identified all the known olfactory transduction components as well as Anoctamin 2 (ANO2). Ano2 transcripts were expressed specifically in OSNs in the olfactory epithelium, and ANO2::EGFP fusion protein localized to the OSN cilia when expressed in vivo using an adenoviral vector. Patch-clamp analysis revealed that ANO2, when expressed in HEK-293 cells, forms a CaCC and exhibits channel properties closely resembling the native olfactory CaCC. Considering these findings together, we propose that ANO2 constitutes the olfactory calcium-activated chloride channel.

MeSH Terms
Animals Anoctamins Cell Line Chloride Channels/metabolism Cilia/metabolism Humans Membrane Proteins/metabolism Mice Olfactory Receptor Neurons/metabolism Patch-Clamp Techniques Proteomics Signal Transduction/physiology Smell/physiology
Chemicals
ANO2 protein, mouse Anoctamins Chloride Channels Membrane Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Stephan Aaron B
Department of Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
Shum Eleen Y
Hirsh Sarah
Cygnar Katherine D
Reisert Johannes
Zhao Haiqing
References (36)
36 references, click to expand
  1. Calmodulin contributes to gating control in olfactory calcium-activated chloride channels.
    J Gen Physiol. 2006 Jun;127(6):737-48 PMID: 16735757
  2. The electrochemical basis of odor transduction in vertebrate olfactory cilia.
    Chem Senses. 2008 Nov;33(9):839-59 PMID: 18703537
  3. Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by a systematic approach.
    Mol Gen Genet. 1999 Dec;262(4-5):683-702 PMID: 10628851
  4. Bestrophin-2 is involved in the generation of intraocular pressure.
    Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1563-70 PMID: 18385076
  5. Mechanism of the excitatory Cl- response in mouse olfactory receptor neurons.
    Neuron. 2005 Feb 17;45(4):553-61 PMID: 15721241
  6. The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia.
    Nat Genet. 2006 Sep;38(9):961-2 PMID: 16940995
  7. TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
    Science. 2008 Oct 24;322(5901):590-4 PMID: 18772398
  8. SEC18/NSF-independent, protein-sorting pathway from the yeast cortical ER to the plasma membrane.
    J Cell Biol. 2005 May 23;169(4):613-22 PMID: 15911878
  9. Expression cloning of TMEM16A as a calcium-activated chloride channel subunit.
    Cell. 2008 Sep 19;134(6):1019-29 PMID: 18805094
  10. Temporal development of cyclic nucleotide-gated and Ca2+ -activated Cl- currents in isolated mouse olfactory sensory neurons.
    J Neurophysiol. 2007 Jul;98(1):153-60 PMID: 17460108
  11. How the olfactory system makes sense of scents.
    Nature. 2001 Sep 13;413(6852):211-8 PMID: 11557990
  12. Chloride accumulation in mammalian olfactory sensory neurons.
    J Neurosci. 2004 Sep 8;24(36):7931-8 PMID: 15356206
  13. Regulation of the cytochrome P450 2A genes.
    Toxicol Appl Pharmacol. 2004 Sep 15;199(3):285-94 PMID: 15364544
  14. Expression of TMEM16 paralogs during murine embryogenesis.
    Dev Dyn. 2008 Sep;237(9):2566-74 PMID: 18729231
  15. Expression patterns of the Tmem16 gene family during cephalic development in the mouse.
    Gene Expr Patterns. 2009 Mar;9(3):178-91 PMID: 19059364
  16. TMEM16A confers receptor-activated calcium-dependent chloride conductance.
    Nature. 2008 Oct 30;455(7217):1210-5 PMID: 18724360
  17. Biochemical studies of the excitable membrane of Paramecium tetraurelia. III. Proteins of cilia and ciliary membranes.
    J Cell Biol. 1980 Mar;84(3):717-38 PMID: 7358796
  18. Olfactory receptor proteins in axonal processes of chemosensory neurons.
    J Neurosci. 2004 Sep 1;24(35):7754-61 PMID: 15342743
  19. A partially purified preparation of isolated chemosensory cilia from the olfactory epithelium of the bullfrog, Rana catesbeiana.
    J Neurosci. 1986 Jul;6(7):1962-9 PMID: 3525776
  20. Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction.
    Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12929-34 PMID: 16912113
  21. Proteomic analysis of a membrane preparation from rat olfactory sensory cilia.
    Chem Senses. 2008 Feb;33(2):145-62 PMID: 18032372
  22. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man.
    Cell. 2001 Jan 26;104(2):205-15 PMID: 11207362
  23. Calcium-activated chloride conductance in frog olfactory cilia.
    J Neurosci. 1991 Nov;11(11):3624-9 PMID: 1941099
  24. Anoctamin/TMEM16 family members are Ca2+-activated Cl- channels.
    J Physiol. 2009 May 15;587(Pt 10):2127-39 PMID: 19015192
  25. The Ca-activated Cl channel and its control in rat olfactory receptor neurons.
    J Gen Physiol. 2003 Sep;122(3):349-63 PMID: 12939394
  26. High-gain, low-noise amplification in olfactory transduction.
    Biophys J. 1997 Aug;73(2):1110-7 PMID: 9251827
  27. Differentially expressed transcripts from phenotypically identified olfactory sensory neurons.
    J Comp Neurol. 2005 Mar 14;483(3):251-62 PMID: 15682396
  28. Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits.
    Science. 2001 Dec 7;294(5549):2176-8 PMID: 11739960
  29. Co-existence of cationic and chloride components in odorant-induced current of vertebrate olfactory receptor cells.
    Nature. 1993 May 6;363(6424):71-4 PMID: 7683113
  30. Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells.
    Nature. 1993 Nov 18;366(6452):283-6 PMID: 8232590
  31. The proteome of rat olfactory sensory cilia.
    Proteomics. 2009 Jan;9(2):322-34 PMID: 19086097
  32. A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3.
    J Thromb Haemost. 2007 Apr;5(4):722-8 PMID: 17371490
  33. Origin of the chloride current in olfactory transduction.
    Neuron. 1993 Jul;11(1):123-32 PMID: 8393322
  34. Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium.
    J Physiol. 2007 Sep 15;583(Pt 3):1005-20 PMID: 17656441
  35. The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD).
    Am J Hum Genet. 2004 Jun;74(6):1255-61 PMID: 15124103
  36. Molecular cloning and characterization of a novel chloride intracellular channel-related protein, parchorin, expressed in water-secreting cells.
    J Biol Chem. 2000 Apr 14;275(15):11164-73 PMID: 10753923
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0903304106
Published
2009-07-14
Epub
2009-00-26
Pages
11776-81
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2702256
Subset
IM
Grants
NIDCD NIH HHS · R01 DC007395 · United States
NIDCD NIH HHS · DC007395 · United States
External Links
PubMed source DOI: 10.1073/pnas.0903304106 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2