In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 1 ( 2013-01-02), p. 360-365
Abstract:
Anoctamin 1 (ANO1)/transmembrane protein 16A (TMEM16A) is a calcium-activated anion channel that may play a role in HCO 3 − secretion in epithelial cells. Here, we report that the anion selectivity of ANO1 is dynamically regulated by the Ca 2+ /calmodulin complex. Whole-cell current measurements in HEK 293T cells indicated that ANO1 becomes highly permeable to HCO 3 − at high [Ca 2+ ] i . Interestingly, this result was not observed in excised patches, indicating the involvement of cytosolic factors in this process. Further studies revealed that the direct association between ANO1 and calmodulin at high [Ca 2+ ] i is responsible for changes in anion permeability. Calmodulin physically interacted with ANO1 in a [Ca 2+ ] i -dependent manner, and addition of recombinant calmodulin to the cytosolic side of excised patches reversibly increased P HCO3 /P Cl . In addition, the high [Ca 2+ ] i -induced increase in HCO 3 − permeability was reproduced in mouse submandibular gland acinar cells, in which ANO1 plays a critical role in fluid secretion. These results indicate that the HCO 3 − permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO 3 − transport, especially in transepithelial HCO 3 − secretion.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1211594110
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2013
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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