Dynamic modulation of ANO1/TMEM16A HCO3- permeability by Ca2+/calmodulin

Jinsei Jung, Joo Hyun Nam, Hyun Woo Park, Uhtaek Oh, Joo Heon Yoon, Min Goo Lee

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

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 [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 [Ca2+]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/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 HCO 3- permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO3- transport, especially in transepithelial HCO3- secretion.

Original languageEnglish
Pages (from-to)360-365
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number1
DOIs
Publication statusPublished - 2013 Jan 2

Fingerprint

Calmodulin
Permeability
Anions
Proteins
Fluids and Secretions
Acinar Cells
Submandibular Gland
HEK293 Cells
Epithelial Cells
Calcium

All Science Journal Classification (ASJC) codes

  • General

Cite this

Jung, Jinsei ; Nam, Joo Hyun ; Park, Hyun Woo ; Oh, Uhtaek ; Yoon, Joo Heon ; Lee, Min Goo. / Dynamic modulation of ANO1/TMEM16A HCO3- permeability by Ca2+/calmodulin. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 1. pp. 360-365.
@article{07f59c9c0f3a4087ab3d19ab9d89ef3f,
title = "Dynamic modulation of ANO1/TMEM16A HCO3- permeability by Ca2+/calmodulin",
abstract = "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 [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 [Ca2+]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/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 HCO 3- permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO3- transport, especially in transepithelial HCO3- secretion.",
author = "Jinsei Jung and Nam, {Joo Hyun} and Park, {Hyun Woo} and Uhtaek Oh and Yoon, {Joo Heon} and Lee, {Min Goo}",
year = "2013",
month = "1",
day = "2",
doi = "10.1073/pnas.1211594110",
language = "English",
volume = "110",
pages = "360--365",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "1",

}

Dynamic modulation of ANO1/TMEM16A HCO3- permeability by Ca2+/calmodulin. / Jung, Jinsei; Nam, Joo Hyun; Park, Hyun Woo; Oh, Uhtaek; Yoon, Joo Heon; Lee, Min Goo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 1, 02.01.2013, p. 360-365.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dynamic modulation of ANO1/TMEM16A HCO3- permeability by Ca2+/calmodulin

AU - Jung, Jinsei

AU - Nam, Joo Hyun

AU - Park, Hyun Woo

AU - Oh, Uhtaek

AU - Yoon, Joo Heon

AU - Lee, Min Goo

PY - 2013/1/2

Y1 - 2013/1/2

N2 - 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 [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 [Ca2+]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/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 HCO 3- permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO3- transport, especially in transepithelial HCO3- secretion.

AB - 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 [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 [Ca2+]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/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 HCO 3- permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO3- transport, especially in transepithelial HCO3- secretion.

UR - http://www.scopus.com/inward/record.url?scp=84871959313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871959313&partnerID=8YFLogxK

U2 - 10.1073/pnas.1211594110

DO - 10.1073/pnas.1211594110

M3 - Article

C2 - 23248295

AN - SCOPUS:84871959313

VL - 110

SP - 360

EP - 365

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 1

ER -