Naslov
Slc26a9 Is Inhibited by the R-region of the Cystic Fibrosis Transmembrane Conductance Regulator via the STAS Domain

Autori
Chang, Min-Hwang ; Plata, Consuelo ; Sinđić, Aleksandra ; Ranatunga, Wasantha K. ; Chen, An-Ping ; Zandi-Nejad, Kambiz ; Chan, Kim W. ; Thompson, James ; Mount, David B. ; Romero, Michael F.

Izvornik
The Journal of biological chemistry (0021-9258) 284 (2009), 41; 28306-28318

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
intracellular pH; voltage clamp; HCO3-; cystic fibrosis; protein interaction

Sažetak
SLC26 proteins function as anion exchangers, channels, and sensors. Previous cellular studies have shown that Slc26a3 and Slc26a6 interact with the R-region of the cystic fibrosis transmembrane conductance regulator (CFTR), (R)CFTR, via the Slc26-STAS (sulfate transporter anti-sigma) domain, resulting in mutual transport activation. We recently showed that Slc26a9 has both nCl(-)-HCO(3)(-) exchanger and Cl(-) channel function. In this study, we show that the purified STAS domain of Slc26a9 (a9STAS) binds purified (R)CFTR. When Slc26a9 and (R)CFTR fragments are co-expressed in Xenopus oocytes, both Slc26a9-mediated nCl(-)-HCO(3)(-) exchange and Cl(-) currents are almost fully inhibited. Deletion of the Slc26a9 STAS domain (a9-DeltaSTAS) virtually eliminated the Cl(-) currents with only a modest affect on nCl(-)-HCO(3)(-) exchange activity. Co-expression of a9-DeltaSTAS and the (R)CFTR fragment did not alter the residual a9-DeltaSTAS function. Replacing the Slc26a9 STAS domain with the Slc26a6 STAS domain (a6-a9-a6) does not change Slc26a9 function and is no longer inhibited by (R)CFTR. These data indicate that the Slc26a9-STAS domain, like other Slc26-STAS domains, binds CFTR in the R-region. However, unlike previously reported data, this binding interaction inhibits Slc26a9 ion transport activity. These results imply that Slc26-STAS domains may all interact with (R)CFTR but that the physiological outcome is specific to differing Slc26 proteins, allowing for dynamic and acute fine tuning of ion transport for various epithelia.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA