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 language | English (US) |
|---|---|
| Pages (from-to) | 1029-1040 |
| Number of pages | 12 |
| Journal | Biochimica et Biophysica Acta - Biomembranes |
| Volume | 1798 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2010 |
Fingerprint
Keywords
- CFTR
- Chloride
- Nonlinear capacitance
- Outer hair cell
- Prestin
- SLC26A
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Cell Biology
Cite this
}
Interaction between CFTR and prestin (SLC26A5). / Homma, Kazuaki; Miller, Katharine K.; Anderson, Charles T.; Sengupta, Soma; Du, Guo Guang; Aguiñaga, Salvador; Cheatham, Mary Ann; Dallos, Peter; Zheng, Jing.
In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1798, No. 6, 01.06.2010, p. 1029-1040.Research output: Contribution to journal › Article
TY - JOUR
T1 - Interaction between CFTR and prestin (SLC26A5)
AU - Homma, Kazuaki
AU - Miller, Katharine K.
AU - Anderson, Charles T.
AU - Sengupta, Soma
AU - Du, Guo Guang
AU - Aguiñaga, Salvador
AU - Cheatham, Mary Ann
AU - Dallos, Peter
AU - Zheng, Jing
PY - 2010/6/1
Y1 - 2010/6/1
N2 - 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.
AB - 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.
KW - CFTR
KW - Chloride
KW - Nonlinear capacitance
KW - Outer hair cell
KW - Prestin
KW - SLC26A
UR - http://www.scopus.com/inward/record.url?scp=77952546525&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952546525&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2010.02.001
DO - 10.1016/j.bbamem.2010.02.001
M3 - Article
VL - 1798
SP - 1029
EP - 1040
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
SN - 0005-2736
IS - 6
ER -