Interaction between CFTR and prestin (SLC26A5)

Kazuaki Homma, Katharine K. Miller, Charles T. Anderson, Soma Sengupta, Guo Guang Du, Salvador Aguiñaga, Mary Ann Cheatham, Peter Dallos, Jing Zheng*

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel that is present in a variety of epithelial cell types, and usually expressed in the luminal membrane. In contrast, prestin (SLC26A5) is a voltage-dependent motor protein, which is present in the basolateral membrane of cochlear outer hair cells (OHCs), and plays an important role in the frequency selectivity and sensitivity of mammalian hearing. By using in situ hybridization and immunofluorescence, we found that both mRNA and protein of CFTR are present in OHCs, and that CFTR localizes in both the apical and the lateral membranes. CFTR was not detected in the lateral membrane of inner hair cells (IHCs) or in that of OHCs derived from prestin-knockout mice, i.e., in instances where prestin is not expressed. These results suggest that prestin may interact physically with CFTR in the lateral membrane of OHCs. Immunoprecipitation experiments confirmed a prestin-CFTR interaction. Because chloride is important for prestin function and for the efferent-mediated inhibition of cochlear output, the prestin-directed localization of CFTR to the lateral membrane of OHCs has a potential physiological significance. Aside from its role as a chloride channel, CFTR is known as a regulator of multiple protein functions, including those of the solute carrier family 26 (SLC26). Because prestin is in the SLC26 family, several members of which interact with CFTR, we explored the potential modulatory relationship associated with a direct, physical interaction between prestin and CFTR. Electrophysiological experiments demonstrated that cAMP-activated CFTR is capable of enhancing voltage-dependent charge displacement, a signature of OHC motility, whereas prestin does not affect the chloride conductance of CFTR.

Original languageEnglish (US)
Pages (from-to)1029-1040
Number of pages12
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1798
Issue number6
DOIs
StatePublished - Jun 1 2010

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Keywords

  • CFTR
  • Chloride
  • Nonlinear capacitance
  • Outer hair cell
  • Prestin
  • SLC26A

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Homma, K., Miller, K. K., Anderson, C. T., Sengupta, S., Du, G. G., Aguiñaga, S., Cheatham, M. A., Dallos, P., & Zheng, J. (2010). Interaction between CFTR and prestin (SLC26A5). Biochimica et Biophysica Acta - Biomembranes, 1798(6), 1029-1040. https://doi.org/10.1016/j.bbamem.2010.02.001