PubMed 25954877

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPP , TRPP2

Title: Polycystin-2 (TRPP2) Regulation by Ca(2+) Is Effected and Diversified by Actin-Binding Proteins.

Authors: María del Rocío Cantero, Horacio F Cantiello

Journal, date & volume: Biophys. J., 2015 May 5 , 108, 2191-200

PubMed link:

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.