Abstract
Cell volume regulation is a fundamental and essential function for mammalian cells to survive. Once cells are exposed to the hypotonic solution, their volume rapidly increases and then gradually returns to the original volume. In the regulatory volume decrease (RVD), swelling-induced activation of the volume-sensitive outwardly rectifying Cl−channel (VSOR) plays an essential role. In the present study, we identified ABCF2, which is a member of ABCF subfamily in the ATP-binding cassette (ABC) transporter superfamily, as the VSOR modulator. Overexpression of ABCF2 in HEK293 cells was found to markedly inhibit swelling-induced activation of VSOR currents. Although expression of the ABCF2 transcripts is reported to be ubiquitous, its function has not been known so far. Therefore, this is the first description about a physiological function of ABCF2. In addition, our immunoprecipitation and immunofluorescence studies demonstrated the protein-protein interaction of ABCF2 and actinin-4 (ACTN4). The ABCF2-ACTN4 interaction was dramatically enhanced under hypotonic conditions. Since ACTN4 is an actin-cross-linking protein, it is possible that ACTN4 provides the molecular link between the actin cytoskeleton and VSOR. [Jpn J Physiol 55 Suppl:S82 (2005)]