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

Loretta Ferrera, Paolo Scudieri, Elvira Sondo, Antonella Caputo, Emanuela Caci, Olga Zegarra-Moran, Roberto Ravazzolo, Luis J V Galietta

Research output: Contribution to journalArticlepeer-review

Abstract

TMEM16A protein, also known as anoctamin-1, has been recently identified as an essential component of Ca2+-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 Ca2+-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.

Original languageEnglish
Pages (from-to)2214-2223
Number of pages10
JournalBBA - Biomembranes
Volume1808
Issue number9
DOIs
Publication statusPublished - Sep 2011

Keywords

  • Alternative splicing
  • Chloride channel
  • Intracellular calcium
  • Patch-clamp

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics

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