Skip to main content
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2008 Feb 7;23(5):293–299. doi: 10.1007/s12264-007-0044-8

Expression of three distinct families of calcium-activated chloride channel genes in the mouse dorsal root ganglion

小鼠背根神经节中三个不同的钙激活氯离子通道基因家族的表达

Mohammed Al-Jumaily 1,, Alexei Kozlenkov 1, Ilana Mechaly 1,2, Agnes Fichard 1,2, Valerie Matha 1, Frederique Scamps 1, Jean Valmier 1,2, Patrick Carroll 1
PMCID: PMC5550578  PMID: 17952139

Abstract

Objective

A calcium-activated chloride current (I Cl(Ca)) has been observed in medium-sized sensory neurons of the dorsal root ganglion (DRG). Axotomy of the sciatic nerve induces a similar current in the majority of medium and large diameter neurons. Our aim is to identify the molecule(s) underlying this current.

Methods

Using conventional and quantitative RT-PCR, we examined the expression in DRG of members of three families of genes, which have been shown to have I Cl(Ca) current inducing properties.

Results

We showed the detection of transcripts representing several members of these families, i.e. chloride channel calcium-activated (CLCA), Bestrophin and Tweety gene families in adult DRG, in the normal state and 3 d after sciatic nerve section, a model for peripheral nerve injury.

Conclusion

Our analysis revealed that that mBest1 and Tweety2 appear as the best candidates to play a role in the injury-induced I Cl(Ca) in DRG neurons.

Keywords: chloride channel calcium activated, bestrophin, tweety, chloride channel, dorsal root ganglion

References

  • [1].Andre S., Boukhaddaoui H., Campo B., Al-Jumaily M., Mayeux V., Greuet D., et al. Axotomy-induced expression of calciumactivated chloride current in subpopulations of mouse dorsal root ganglion neurons. J Neurophysiol. 2003;90:3764–3773. doi: 10.1152/jn.00449.2003. [DOI] [PubMed] [Google Scholar]
  • [2].Campbell H.D., Kamei M., Claudianos C., Woollatt E., Sutherland G.R., Suzuki Y., et al. Human and mouse homologues of the Drosophila melanogaster tweety (tty) gene: a novel gene family encoding predicted transmembrane proteins. Genomics. 2000;68:89–92. doi: 10.1006/geno.2000.6259. [DOI] [PubMed] [Google Scholar]
  • [3].Chien L.T., Zhang Z.R., Hartzell H.C. Single Cl-channels activated by Ca2+ in Drosophila S2 cells are mediated by bestrophins. J Gen Physiol. 2006;128:247–259. doi: 10.1085/jgp.200609581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4].Frings S., Reuter D., Kleene S.J. Neuronal Ca2+-activated Cl-channels—homing in on an elusive channel species. Prog Neurobiol. 2000;60:247–289. doi: 10.1016/S0301-0082(99)00027-1. [DOI] [PubMed] [Google Scholar]
  • [5].Fuller C.M., Ji H.L., Tousson A., Elble R.C., Pauli B.U., Benos D.J. Ca (2+)-activated Cl(−) channels: a newly emerging anion transport family. Pflugers Arch. 2001;443(Suppl1):S107–S110. doi: 10.1007/s004240100655. [DOI] [PubMed] [Google Scholar]
  • [6].Gibson A., Lewis A.P., Affleck K., Aitken A.J., Meldrum E., Thompson N. hCLCA1 and mCLCA3 are secreted non-integral membrane proteins and therefore are not ion channels. J Biol Chem. 2005;280:27205–27212. doi: 10.1074/jbc.M504654200. [DOI] [PubMed] [Google Scholar]
  • [7].Greenwood I.A., Leblanc N. Overlapping pharmacology of Ca2+-activated Cl-and K+ channels. Trends Pharmacol Sci. 2007;28:1–5. doi: 10.1016/j.tips.2006.11.004. [DOI] [PubMed] [Google Scholar]
  • [8].Gruber A.D., Elble R.C., Pauli B.U. Discovery and cloning of the CLCA gene family. In: Fuller C.M., editor. Current topics in Membranes. London: Academic Press; 2002. pp. 367–387. [Google Scholar]
  • [9].Hartzell C., Putzier I., Arreola J. Calcium-activated chloride channels. Annu Rev Physiol. 2005;67:719–758. doi: 10.1146/annurev.physiol.67.032003.154341. [DOI] [PubMed] [Google Scholar]
  • [10].Thompson J.D., Higgins D.G., Gibson T.J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994;22:4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Hilaire C., Inquimbert P., Al-Jumaily M., Greuet D., Valmier J., Scamps F. Calcium dependence of axotomized sensory neurons excitability. Neurosci Lett. 2005;380:330–334. doi: 10.1016/j.neulet.2005.01.068. [DOI] [PubMed] [Google Scholar]
  • [12].Hoebeeck J., van der Luijt R., Poppe B., De Smet E., Yigit N., Claes K., et al. Rapid detection of VHL exon deletions using real-time quantitative PCR. Lab Invest. 2005;85:24–33. doi: 10.1038/labinvest.3700209. [DOI] [PubMed] [Google Scholar]
  • [13].Jentsch T.J., Stein V., Weinreich F., Zdebik A.A. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002;82:503–568. doi: 10.1152/physrev.00029.2001. [DOI] [PubMed] [Google Scholar]
  • [14].Kramer F., Stohr H., Weber B.H. Cloning and characterization of the murine Vmd2 RFP-TM gene family. Cytogenet Genome Res. 2004;105:107–114. doi: 10.1159/000078016. [DOI] [PubMed] [Google Scholar]
  • [15].Leverkoehne I., Horstmeier B.A., von Samson-Himmelstjerna G., Scholte B.J., Gruber A.D. Real-time RT-PCR quantitation of mCLCA1 and mCLCA2 reveals differentially regulated expression in pre-and postnatal murine tissues. Histochem Cell Biol. 2002;118:11–17. doi: 10.1007/s00418-002-0420-4. [DOI] [PubMed] [Google Scholar]
  • [16].Loewen M.E., Forsyth G.W. Structure and function of CLCA proteins. Physiol Rev. 2005;85:1061–1092. doi: 10.1152/physrev.00016.2004. [DOI] [PubMed] [Google Scholar]
  • [17].Marmorstein A.D., Marmorstein L.Y., Rayborn M., Wang X., Hollyfield J.G., Petrukhin K. Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium. Proc Natl Acad Sci U S A. 2000;97:12758–12763. doi: 10.1073/pnas.220402097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Matthews C.A., Shaw J.E., Hooper J.A., Young I.G., Crouch M.F., Campbell H.D. Expression and evolution of the mammalian brain gene Ttyh1. J Neurochem. 2007;100:693–707. doi: 10.1111/j.1471-4159.2006.04237.x. [DOI] [PubMed] [Google Scholar]
  • [19].Mechaly I., Bourane S., Piquemal D., Al-Jumaily M., Ventéo S., Puech S., et al. Gene profiling during development and after a peripheral nerve traumatism reveals genes specifically induced by injury in dorsal root ganglia. Mol Cell Neurosci. 2006;32:217–229. doi: 10.1016/j.mcn.2006.04.004. [DOI] [PubMed] [Google Scholar]
  • [20].Mundhenk L., Alfalah M., Elble R.C., Pauli B.U., Naim H.Y., Gruber A.D. Both cleavage products of the mCLCA3 protein are secreted soluble proteins. J Biol Chem. 2006;281:30072–30080. doi: 10.1074/jbc.M606489200. [DOI] [PubMed] [Google Scholar]
  • [21].Needleman S.B., Wunsch C.D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970;48:443–453. doi: 10.1016/0022-2836(70)90057-4. [DOI] [PubMed] [Google Scholar]
  • [22].Ritzka M., Weinel C., Stanke F., Tummler B. Sequence comparison of the whole murine and human CLCA locus reveals conserved synteny between both species. Genome Lett. 2003;2:149–154. doi: 10.1166/gl.2003.034. [DOI] [Google Scholar]
  • [23].Suzuki M., Mizuno A. A novel human Cl(-) channel family related to Drosophila flightless locus. J Biol Chem. 2004;279:22461–22468. doi: 10.1074/jbc.M313813200. [DOI] [PubMed] [Google Scholar]
  • [24].Suzuki M. The Drosophila tweety family: molecular candidates for large-conductance Ca2+-activated Cl-channels. Exp Physiol. 2006;91:141–147. doi: 10.1113/expphysiol.2005.031773. [DOI] [PubMed] [Google Scholar]
  • [25].Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002, 3: RESEARCH0034. [DOI] [PMC free article] [PubMed]
  • [26].Whittaker C.A., Hynes R.O. Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere. Mol Biol Cell. 2002;13:3369–3387. doi: 10.1091/mbc.E02-05-0259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [27].Yu K., Cui Y., Hartzell H.C. The bestrophin mutation A243V, linked to adult-onset vitelliform macular dystrophy, impairs its chloride channel function. Invest Ophthalmol Vis Sci. 2006;47:4956–4961. doi: 10.1167/iovs.06-0524. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES