ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins

Am J Physiol Cell Physiol. 2012 Feb 1;302(3):C482-93. doi: 10.1152/ajpcell.00140.2011. Epub 2011 Nov 9.


Ca(2+)-activated Cl(-) channels (CaCCs) participate in numerous physiological functions such as neuronal excitability, sensory transduction, and transepithelial fluid transport. Recently, it was shown that heterologously expressed anoctamins ANO1 and ANO2 generate currents that resemble native CaCCs. The anoctamin family (also called Tmem16) consists of 10 members, but it is not known whether all members of the family are CaCCs. Expression of ANOs 3-7 in HEK293 cells did not generate Cl(-) currents activated by intracellular Ca(2+), as determined by whole cell patch clamp electrophysiology. With the use of confocal imaging, only ANO1 and ANO2 traffic to the plasma membrane when expressed heterologously. Furthermore, endogenously expressed ANO7 in the human prostate is predominantly intracellular. We took a chimeric approach to identify regions critical for channel trafficking and function. However, none of the chimeras of ANO1 and ANO5/7 that we made trafficked to the plasma membrane. Our results suggest that intracellular anoctamins may be endoplasmic reticulum proteins, although it remains unknown whether these family members are CaCCs. Determining the role of anoctamin family members in ion transport will be critical to understanding their functions in physiology and disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anoctamin-1
  • Anoctamins
  • Biological Transport / physiology
  • COS Cells
  • Cell Line
  • Cell Membrane / metabolism
  • Chimera
  • Chloride Channels / biosynthesis
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Chlorocebus aethiops
  • Endoplasmic Reticulum / physiology*
  • HEK293 Cells
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Patch-Clamp Techniques
  • Prostate / metabolism
  • Recombinant Fusion Proteins / metabolism


  • ANO1 protein, human
  • ANO1 protein, mouse
  • ANO7 protein, human
  • Anoctamin-1
  • Anoctamins
  • Chloride Channels
  • Membrane Proteins
  • Neoplasm Proteins
  • Recombinant Fusion Proteins