A variant of the Ca2+-activated Cl channel Best3 is expressed in mouse exocrine glands

Srivastava, Alaka; Romanenko, Victor G.; Gonzalez-Begne, Mireya; Catalan, Marcelo A.; Melvin, James E.

Abstract

Fluid secretion by exocrine glands requires the activation of an apical Ca2+-dependent Cl channel, the molecular identity of which is unknown. We found that mouse exocrine glands expressed an alternately spliced variant of Best3, a member of the Bestrophin ( Vmd2) Ca2+-activated Cl channel gene family, whereas the heart expressed full-length Best3. The spliced transcript lacked exons 2, 3 and 6 ( Best3-Delta 2,3,6) and is predicted to generate an in-frame protein missing the entire cytoplasmic N terminus, the initial two transmembrane domains and part of the first intracellular loop. In addition to exocrine glands, the Best3-Delta 2,3,6 splice variant transcript was detected in lung, testis and kidney. The parotid gland and heart expressed proteins of the predicted size for Best3-Delta 2,3,6 and full-length Best3, respectively, that targeted to the plasma membrane in HEK293 cells. HEK293 cells expressing Best3 displayed Ca2+-dependent Cl- currents that were sensitive to the Cl channel blocker DIDS. In contrast, no Ca2+-dependent Cl- currents were detected in cells expressing Best3-Delta 2,3,6. Cotransfection of Best3-Delta 2,3,6 with Best3 or Best2 ( also expressed in salivary gland acinar cells) had no significant effects on the currents generated by either of these Ca2+-dependent Cl channels. Our results demonstrate that exocrine glands express a unique splice variant of Best3. Nevertheless, Best3- Delta 2,3,6 does not produce Ca2+- dependent Cl- currents, nor does it regulate the activity of Best2 or the full-length Best3 channel.

Más información

Título según WOS: ID WOS:000255746500004 Not found in local WOS DB
Título de la Revista: JOURNAL OF MEMBRANE BIOLOGY
Volumen: 222
Número: 1
Editorial: Springer-Verlag
Fecha de publicación: 2008
Página de inicio: 43
Página final: 54
DOI:

10.1007/s00232-008-9098-4

Notas: ISI