The nhTMEM16 Scramblase Is Also a Nonselective Ion Channel Academic Article uri icon


MeSH Major

  • Fungal Proteins
  • Hypocreales
  • Ion Channels
  • Phospholipid Transfer Proteins


  • The TMEM16 family comprises Ca(2+)-activated Cl(-) channels and phospholipid scramblases. The crystal structure of a fungal homolog, nhTMEM16, revealed an important architectural feature of this protein family in the form of a bilayer-spanning hydrophilic groove that is directly exposed to the membrane. This groove likely provides a pathway for lipid translocation. As mutations that alter ion channel activity of the TMEM16 proteins localize around the groove, it was suggested that the ion and lipid pathways coincide such that the ion pore is partly lined by phospholipids. However, this proposal was not supported by the observation that nhTMEM16 does not mediate ion transport. Here we show that nhTMEM16 mediates both ion and lipid transport and that its properties closely resemble those of a previously characterized fungal homolog, afTMEM16. We show that the reported lack of ion transport activity of nhTMEM16 is due to the lipid composition of the reconstitution membranes and to the┬ápresence of a GFP tag. Thus, nhTMEM16, like afTMEM16 and the mammalian TMEM16F, mediates simultaneous lipid scrambling and nonspecific ion transport. This supports the hypothesis that these two processes are tightly correlated and likely to be a general functional feature of the TMEM16 scramblases and therefore of general importance in understanding their biological roles.

publication date

  • November 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC5103024

Digital Object Identifier (DOI)

  • 10.1016/j.bpj.2016.09.032

PubMed ID

  • 27806273

Additional Document Info

start page

  • 1919

end page

  • 1924


  • 111


  • 9