title: Polycystin-2 (TRPP2) Regulation by Ca(2+) Is Effected and Diversified by Actin-Binding Proteins.
abstract: Calcium regulation of Ca(2+)-permeable ion channels is an important mechanism in the control of cell function. Polycystin-2 (PC2, TRPP2), a member of the transient receptor potential superfamily, is a nonselective cation channel with Ca(2+) permeability. The molecular mechanisms associated with PC2 regulation by Ca(2+) remain ill-defined. We recently demonstrated that PC2 from human syncytiotrophoblast (PC2hst) but not the in vitro translated protein (PC2(iv)), functionally responds to changes in intracellular (cis) Ca(2+). In this study we determined the regulatory effect(s) of Ca(2+)-sensitive and -insensitive actin-binding proteins (ABPs) on PC2(iv) channel function in a lipid bilayer system. The actin-bundling protein α-actinin increased PC2(iv) channel function in the presence of cis Ca(2+), although instead was inhibitory in its absence. Conversely, filamin that shares actin-binding domains with α-actinin had a strong inhibitory effect on PC2(iv) channel function in the presence, but no effect in the absence of cis Ca(2+). Gelsolin stimulated PC2(iv) channel function in the presence, but not the absence of cis Ca(2+). In contrast, profilin that shares actin-binding domains with gelsolin, significantly increased PC2(iv) channel function both in the presence and absence of Ca(2+). The distinct effect(s) of the ABPs on PC2(iv) channel function demonstrate that Ca(2+) regulation of PC2 is actually mediated by direct interaction(s) with structural elements of the actin cytoskeleton. These data indicate that specific ABP-PC2 complexes would confer distinct Ca(2+)-sensitive properties to the channel providing functional diversity to the cytoskeletal control of transient receptor potential channel regulation.
authors.affiliation: Cátedra de Biofísica, Facultad de Odontología, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: María del Rocío
authors.initials: Mdel R
authors.lastname: Cantero
authors.affiliation: Cátedra de Biofísica, Facultad de Odontología, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: hcantiello@yahoo.com.ar.
authors.forename: Horacio F
authors.initials: HF
authors.lastname: Cantiello
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D011485:Protein Binding; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D002118:Calcium; D008051:Lipid Bilayers; D008840:Microfilament Proteins; D050396:TRPP Cation Channels