Interaction of epithelial ion channels with the actin-based cytoskeleton

Abstract

The interaction of ion channels with the actin-based cytoskeleton in epithelial cells not only maintains the polarized expression of ion channels within specific membrane domains, it also functions in the intracellular trafficking and regulation of channel activity. Initial evidence supporting an interaction between epithelial ion channels and the actin-based cytoskeleton came from patch-clamp studies examining the effects of cytochalasins on channel activity. Cytochalasins were shown to either activate or inactivate epithelial ion channels. An interaction between the actin-based cytoskeleton and epithelial ion channels was further supported by the fact that the addition of monomeric or filamentous actin to excised patches had an effect on channel activity comparable to that of cytochalasins. Through the recent application of molecular and proteomic approaches, we now know that the interactions between epithelial ion channels and actin can either be direct or indirect, the latter being mediated through scaffolding or actin-binding proteins that serve as links between the channels and the actin-based cytoskeleton. This review discusses recent advances in our understanding of the interactions between epithelial ion channels and the actin-based cytoskeleton, and the roles these interactions play in regulating the cell surface expression, activity, and intracellular trafficking of epithelial ion channels.

Anoctamin 1 (Tmem16A) Ca 2 + -activated chloride channel stoichiometrically interacts with an ezrin–radixin–moesin network

“…It has been reported that both depolymerization of the actin cytoskeleton with cytochalasin-D and stabilization of the actin network with phalloidin suppresses Ano1 currents (42). A number of ion channels have been shown to interact with the actin cytoskeleton (43). It is particularly interesting that another epithelial Cl − channel, CFTR, interacts with some of the same proteins that Ano1 interacts with, notably ezrin and NHERF1.…”

HE6/GPR64 adhesion receptor co-localizes with apical and subapical F-actin scaffold in male excurrent duct epithelia

“…Actin microfilaments are responsible for surface expression, functional activity and intracellular trafficking of numerous ion channels (for a review, see Mazzochi et al 2006). They may also be involved in the targeting and/or internalization of surface receptors, including HE6/ GPR64.…”

Comparison of cellular effects of starch-coated SPIONs and poly(lactic-co-glycolic acid) matrix nanoparticles on human monocytes

“…That nanoparticles can have a regulatory impact on ion channels was shown for SiO 2 nanoparticles on TRP4 channels in a neuronal cell line. 52 Ion channels are tightly connected to the cytoskeleton, especially to the actin fibers, 19 either through bindings between specialized proteins and the fibers 53 or through interaction between fibers and lipid rafts, in which the channels can be located. 20 These connections allow the channels to maintain their function in the fluidic environment of the membrane.…”