IndraLab

"The cytoplasmic scaffolding protein filamin A (FilA) interacts with HCN1 and influences its membrane expression and localization ( xref )."

"Importantly, filamin A binds HCN1 through a distinct sequence in the channel C’ terminus, while not being able to interact with either HCN2 or the HCN4 channel isoform [ xref ]."

"Our current efforts focus on investigating the potential role of HCN1-filamin interactions in neurons, and the cellular pathways by which this regulation takes place."

"Through the use of a yeast two-hybrid technique, here we showed that filamin A interacts with HCN1, an HCN isoform widely expressed in the brain, but not with HCN2 or HCN4."

"The interaction of HCN1 with filamin A appears to cluster HCN1 protein on cell membranes and decrease I h conductance in a melanoma cell line. xref As noted above in discussing effects on gating and kinetics, the role of filamin A in h channel surface expression and clustering in neurons is yet to be explored."

"We also verified by immunoprecipitation from bovine brain that the filamin A-HCN1 interaction is functional in vivo."

"Interaction of filamin A with HCN1 in melanoma-derived cell lines results in clustering of the channels on the cell surface and reduced current density [ xref ]."

"Furthermore, acute abrogation of HCN1-FLNa interaction in neurons, with the use of decoy peptides that mimic the FLNa-binding domain of HCN1, abolishes the punctate distribution of HCN1 channels in neuronal cell bodies, augments endogenous Ih, and enhances the rebound-response ("voltage-sag") of the neuronal membrane to transient hyperpolarizing events."

"Filamin A is a large cytoskeletal protein capable of binding actin, and contains 24 immunoglobin-like repeats and an actin-binding site at the N-terminus. xref , xref It has been reported to interact with multiple ligand- and voltage-gated ion channels, including the dopamine receptors D 2 and D 3 , xref K V 4.2, xref and K ir 2.1. xref Similarly to KCNE2, in addition to binding to voltage-gated potassium channels, filamin A also binds the HCN1 C-terminus via its final two Ig-like repeats. xref Filamin A did not interact with HCN2 or HCN4, and bound a 22 amino acid (amino acids 694–715) region distal to the HCN1 CNBD. xref "