A minimal isoform of the TMEM16A protein associated with chloride channel activity

Biochim Biophys Acta. 2011 Sep;1808(9):2214-23. doi: 10.1016/j.bbamem.2011.05.017. Epub 2011 May 30.


TMEM16A protein, also known as anoctamin-1, has been recently identified as an essential component of Ca(2+)-activated Cl(-) channels. We previously reported the existence of different TMEM16A isoforms generated by alternative splicing. In the present study, we have determined the functional properties of a minimal TMEM16A protein. This isoform, called TMEM16A(0), has a significantly shortened amino-terminus and lacks three alternative segments localized in the intracellular regions of the protein (total length: 840 amino acids). TMEM16A(0) expression is associated with Ca(2+)-activated Cl(-) channel activity as measured by three different functional assays based on the halide-sensitive yellow fluorescent protein, short-circuit current recordings, and patch-clamp technique. However, compared to a longer isoform, TMEM16(abc) (total length: 982 amino acids), TMEM16A(0) completely lacks voltage-dependent activation. Furthermore, TMEM16A(0) and TMEM16A(abc) have similar but not identical responses to extracellular anion replacement, thus suggesting a difference in ion selectivity and conductance. Our results indicate that TMEM16A(0) has the basic domains required for anion transport and Ca(2+)-sensitivity. However, the absence of alternative segments, which are present in more complex isoforms of TMEM16A, modifies the channel gating and ion transport ability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Anoctamin-1
  • Bacterial Proteins / metabolism
  • Calcium / chemistry
  • Chloride Channels / chemistry*
  • Chlorides / pharmacology
  • HEK293 Cells
  • Humans
  • Ions
  • Luminescent Proteins / metabolism
  • Membrane Potentials
  • Membrane Proteins / chemistry*
  • Microscopy, Fluorescence / methods
  • Neoplasm Proteins / chemistry*
  • Patch-Clamp Techniques
  • Protein Conformation
  • Protein Isoforms
  • Transfection


  • ANO1 protein, human
  • Anoctamin-1
  • Bacterial Proteins
  • Chloride Channels
  • Chlorides
  • Ions
  • Luminescent Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • Protein Isoforms
  • yellow fluorescent protein, Bacteria
  • Calcium