Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 1, Pages 360-365Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1211594110
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Funding
- National Research Foundation
- Ministry of Education, Science, and Technology (Korea) [2011-0001178, 2011-0016484]
- National Project for Personalized Genomic Medicine, Korea Health 21 R&D Project, Ministry of Health & Welfare (Korea) [A111218-11-PG03]
- National Research Foundation of Korea [R31-2012-000-10103-0, 2007-0056092, 2010-0017752] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Anoctamin 1 (ANO1)/transmembrane protein 16A (TMEM16A) is a calcium-activated anion channel that may play a role in HCO3- secretion in epithelial cells. Here, we report that the anion selectivity of ANO1 is dynamically regulated by the Ca2+/calmodulin complex. Whole-cell current measurements in HEK 293T cells indicated that ANO1 becomes highly permeable to HCO3- at high [Ca2+](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 [Ca2+](i) is responsible for changes in anion permeability. Calmodulin physically interacted with ANO1 in a [Ca2+](i)-dependent manner, and addition of recombinant calmodulin to the cytosolic side of excised patches reversibly increased P-HCO3/PCl. In addition, the high [Ca2+](i)-induced increase in HCO3- permeability was reproduced in mouse submandibular gland acinar cells, in which ANO1 plays a critical role in fluid secretion. These results indicate that the HCO3- permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO3- transport, especially in transepithelial HCO3- secretion.
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