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Molecular functions of anoctamin 6 (TMEM16F): a chloride channel, cation channel, or phospholipid scramblase?

  • Karl KunzelmannEmail author
  • Bernd Nilius
  • Grzegorz Owsianik
  • Rainer Schreiber
  • Jiraporn Ousingsawat
  • Lalida Sirianant
  • Podchanart Wanitchakool
  • Edouard M. Bevers
  • Johan W. M. Heemskerk
Invited Review

Abstract

Anoctamin 6 (Ano6; TMEM16F gene) is a ubiquitous protein; the expression of which is defective in patients with Scott syndrome, an inherited bleeding disorder based on defective scrambling of plasma membrane phospholipids. For Ano6, quite diverse functions have been described: (1) it can form an outwardly rectifying, Ca2+-dependent and a volume-regulated Cl channel; (2) it was claimed to be a Ca2+-regulated nonselective cation channel permeable for Ca2+; (3) it was shown to be essential for Ca2+-mediated scrambling of membrane phospholipids; and (4) it can regulate cell blebbing and microparticle shedding. Deficiency of Ano6 in blood cells from Scott patients or Ano6 null mice appears to affect all of these cell responses. Furthermore, Ano6 deficiency in mice impairs the mineralization of osteoblasts, resulting in reduced skeletal development. These diverse results have been obtained under different experimental conditions, which may explain some of the contradictions. This review therefore aims to summarize the currently available information on the diverse roles of Ano6 and tries to clear up some of the existing controversies.

Keywords

TMEM16F Anoctamin 6 Ano6 Scott syndrome Cation channels Chloride channels Phospholipid scrambling 

Notes

Acknowledgments

This work was supported by DFG SFB699 (KK, JO, RS, LS, PW) and the Cardiovascular Center of Maastricht University (EB, JH) and by grants from the Belgian Federal Government (IUAP P6/28 and P7/13), the Research Foundation-Flanders (F.W.O., G.0565.07 and G.0A61.13), and the Research Council of the KU Leuven (GOA 2009/07, EF/95/010 and PF-TRPLe) (GO, BN).

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Karl Kunzelmann
    • 1
    Email author
  • Bernd Nilius
    • 2
  • Grzegorz Owsianik
    • 2
  • Rainer Schreiber
    • 1
  • Jiraporn Ousingsawat
    • 1
  • Lalida Sirianant
    • 1
  • Podchanart Wanitchakool
    • 1
  • Edouard M. Bevers
    • 3
  • Johan W. M. Heemskerk
    • 3
  1. 1.Institut für PhysiologieUniversität RegensburgRegensburgGermany
  2. 2.Laboratory of Ion Channel Research, Department of Cellular and Molecular MedicineKU LeuvenLeuvenBelgium
  3. 3.Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM)University of MaastrichtMaastrichtThe Netherlands

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