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

Karl Kunzelmann*, Bernd Nilius, Grzegorz Owsianik, Rainer Schreiber, Jiraporn Ousingsawat, Lalida Sirianant, Podchanart Wanitchakool, Edouard M. Bevers, Johan W. M. Heemskerk

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.
Original languageEnglish
Pages (from-to)407-414
JournalPflugers Archiv-European Journal of Physiology
Volume466
Issue number3
DOIs
Publication statusPublished - Mar 2014

Keywords

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

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