Structural interaction and functional regulation of polycystin-2 by filamin.

Structural interaction and functional regulation of polycystin-2 by filamin.

Blog Article

Filamins are important actin cross-linking proteins implicated in scaffolding, membrane stabilization and signal transduction, through interaction with ion channels, receptors and signaling proteins.Here we report the physical and functional interaction between filamins and polycystin-2, a TRP-type cation channel here mutated in 10-15% patients with autosomal dominant polycystic kidney disease.Yeast two-hybrid and GST pull-down experiments demonstrated that the C-termini of filamin isoforms A, B and C directly bind to both the intracellular N- and C-termini of polycystin-2.Reciprocal co-immunoprecipitation experiments showed that endogenous polycystin-2 and filamins are in the same complexes in renal epithelial cells and human melanoma A7 cells.We then examined the effect of filamin on polycystin-2 channel function by electrophysiology studies with a lipid bilayer reconstitution system and found that filamin-A substantially inhibits polycystin-2 channel activity.

Our study indicates that animationbengal.com filamins are important regulators of polycystin-2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein.