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Modulating Ca2+ signals: a common theme for TMEM16, Ist2, and TMC

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Abstract

Since the discovery of TMEM16A (anoctamin 1, ANO1) as Ca2+-activated Cl− channel, the protein was found to serve different physiological functions, depending on the type of tissue. Subsequent reports on other members of the anoctamin family demonstrated a broad range of yet poorly understood properties. Compromised anoctamin function is causing a wide range of diseases, such as hearing loss (ANO2), bleeding disorder (ANO6), ataxia and dystonia (ANO3, 10), persistent borrelia and mycobacteria infection (ANO10), skeletal syndromes like gnathodiaphyseal dysplasia and limb girdle muscle dystrophy (ANO5), and cancer (ANO1, 6, 7). Animal models demonstrate CF-like airway disease, asthma, and intestinal hyposecretion (ANO1). Although present data indicate that ANO1 is a Ca2+-activated Cl− channel, it remains unclear whether all anoctamins form plasma membrane-localized or intracellular chloride channels. We find Ca2+-activated Cl− currents appearing by expression of most anoctamin paralogs, including the Nectria haematococca homologue nhTMEM16 and the yeast homologue Ist2. As recent studies show a role of anoctamins, Ist2, and the related transmembrane channel-like (TMC) proteins for intracellular Ca2+ signaling, we will discuss the role of these proteins in generating compartmentalized Ca2+ signals, which may give a hint as to the broad range of cellular functions of anoctamins.

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Acknowledgments

The work of the Kunzelmann laboratory is funded by Cystic Fibrosis Trust SRC 003, INOVCF, DFG SFB699-A7/A12, DFG KU756/12-1, and Volkswagenstiftung AZ 87 499. We thank Dr. J. Brunner, Department of Biochemistry, University of Zurich, Switzerland, for providing the nhTMEM16 cDNA.

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  1. Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany

    Karl Kunzelmann, Ines Cabrita, Podchanart Wanitchakool, Jiraporn Ousingsawat, Lalida Sirianant, Roberta Benedetto & Rainer Schreiber

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  1. Karl Kunzelmann
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  2. Ines Cabrita
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Correspondence to Karl Kunzelmann.

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Kunzelmann, K., Cabrita, I., Wanitchakool, P. et al. Modulating Ca2+ signals: a common theme for TMEM16, Ist2, and TMC. Pflugers Arch - Eur J Physiol 468, 475–490 (2016). https://doi.org/10.1007/s00424-015-1767-4

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  • DOI: https://doi.org/10.1007/s00424-015-1767-4

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