title: Molecular functions of anoctamin 6 (TMEM16F): a chloride channel, cation channel, or phospholipid scramblase?
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, Ca(2+)-dependent and a volume-regulated Cl(-) channel; (2) it was claimed to be a Ca(2+)-regulated nonselective cation channel permeable for Ca(2+); (3) it was shown to be essential for Ca(2+)-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.
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany, karl.kunzelmann@vkl.uni-regensburg.de.
authors.forename: Karl
authors.initials: K
authors.lastname: Kunzelmann
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Owsianik
authors.forename: Rainer
authors.initials: R
authors.lastname: Schreiber
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Ousingsawat
authors.forename: Lalida
authors.initials: L
authors.lastname: Sirianant
authors.forename: Podchanart
authors.initials: P
authors.lastname: Wanitchakool
authors.forename: Edouard M
authors.initials: EM
authors.lastname: Bevers
authors.forename: Johan W M
authors.initials: JW
authors.lastname: Heemskerk
mesh_terms: D000818:Animals; D000075368:Anoctamins; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
chemical_list: C576687:ANO6 protein, mouse; C555078:ANO6 protein, human; D000075368:Anoctamins; D002712:Chlorides; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D002118:Calcium