Allosteric modulation of alternatively spliced Ca2+ -activated Cl- channels TMEM16A by PI(4,5)P2 and CaMKII

Proceedings of the National Academy of Sciences of the United States of America
Woori KoByung-Chang Suh

Abstract

Transmembrane 16A (TMEM16A, anoctamin1), 1 of 10 TMEM16 family proteins, is a Cl- channel activated by intracellular Ca2+ and membrane voltage. This channel is also regulated by the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. We find that two splice variants of TMEM16A show different sensitivity to endogenous PI(4,5)P2 degradation, where TMEM16A(ac) displays higher channel activity and more current inhibition by PI(4,5)P2 depletion than TMEM16A(a). These two channel isoforms differ in the alternative splicing of the c-segment (exon 13). The current amplitude and PI(4,5)P2 sensitivity of both TMEM16A(ac) and (a) are significantly strengthened by decreased free cytosolic ATP and by conditions that decrease phosphorylation by Ca2+/calmodulin-dependent protein kinase II (CaMKII). Noise analysis suggests that the augmentation of currents is due to a rise of single-channel current (i), but not of channel number (N) or open probability (PO). Mutagenesis points to arginine 486 in the first intracellular loop as a putative binding site for PI(4,5)P2, and to serine 673 in the third intracellular loop as a site for regulatory channel phosphorylation that modulates the action of PI(4,5)P2 In silico simulation s...Continue Reading

References

Jan 1, 1992·Methods in Enzymology·S H Heinemann, F Conti
Oct 1, 1995·Kidney International·I I Ismailov, D J Benos
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·V DerkachT R Soderling
Nov 22, 2002·Advances in Physiology Education·Osvaldo AlvarezRamon Latorre
May 20, 2005·Nature·Yoshimichi MurataYasushi Okamura
Jun 1, 2005·Current Opinion in Neurobiology·Byung-Chang Suh, Bertil Hille
Jun 28, 2006·The Journal of General Physiology·Jeff E AngermannIain A Greenwood
Jun 25, 2008·Annual Review of Biophysics·Byung-Chang Suh, Bertil Hille
Aug 12, 2008·Channels·Coeli M B LopesDiomedes E Logothetis
Sep 23, 2008·Cell·Björn Christian SchroederLily Yeh Jan
Dec 17, 2008·The Journal of Physiology·Yasushi OkamuraHirohide Iwasaki
Sep 29, 2009·Cell Calcium·Karl KunzelmannRainer Schreiber
Oct 13, 2009·The Journal of Biological Chemistry·Loretta FerreraLuis J V Galietta
Feb 23, 2010·Cardiovascular Research·William R SonesIain A Greenwood
Aug 6, 2010·American Journal of Physiology. Cell Physiology·Alison J DavisNormand Leblanc
Dec 1, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yuemin TianKarl Kunzelmann
Jan 7, 2011·American Journal of Physiology. Cell Physiology·Kenneth W DunnJohn H McDonald
May 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Qinghuan XiaoH Criss Hartzell
Jun 8, 2011·Biochimica Et Biophysica Acta·Loretta FerreraLuis J V Galietta
Aug 10, 2011·BMC Molecular Biology·Kate E O'DriscollFiona C Britton
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Dec 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jinsei JungMin Goo Lee
Apr 25, 2013·The Journal of Physiology·Aiste AdomavicienePaolo Tammaro
Jun 7, 2013·Nature·Matthew R Whorton, Roderick MacKinnon
Oct 2, 2013·The Journal of General Physiology·Kerstin VockeFrank Möhrlen
Feb 12, 2014·Biochimica Et Biophysica Acta·Marina A KasimovaLucie Delemotte
Apr 3, 2014·Physiological Reviews·Nicoletta Pedemonte, Luis J V Galietta
Aug 12, 2014·Nature Chemical Biology·Miao ZhangJi-Fang Zhang
Sep 23, 2014·Biochimica Et Biophysica Acta·Bertil HilleByung-Chang Suh
Dec 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Tingting YangHenry M Colecraft
Dec 31, 2014·Nature Methods·Jianyi YangYang Zhang
Jan 13, 2015·British Journal of Pharmacology·Sarah K BurrisJonathan H Jaggar
Jan 31, 2015·Biochimica Et Biophysica Acta·Scott B Hansen
Jul 18, 2015·Cell Calcium·Hyeyeon ChunUhtaek Oh
Sep 15, 2015·Science Advances·Miao ZhangDiomedes E Logothetis
Nov 7, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Amal K DuttaAndrew P Feranchak
Nov 13, 2015·British Journal of Pharmacology·Chau M TaPaolo Tammaro
Jan 8, 2016·Pflügers Archiv : European journal of physiology·Jarred M Whitlock, H Criss Hartzell
Jul 15, 2016·American Journal of Physiology. Cell Physiology·Tae Sik SungKenton M Sanders

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May 1, 2021·International Journal of Molecular Sciences·Woori Ko, Byung-Chang Suh

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