Signaling Enzymes and Ion Channels Being Modulated by the Actin Cytoskeleton at the Plasma Membrane

Abstract

A cell should deal with the changing external environment or the neighboring cells. Inevitably, the cell surface receives and transduces a number of signals to produce apt responses. Typically, cell surface receptors are activated, and during this process, the subplasmalemmal actin cytoskeleton is often rearranged. An intriguing point is that some signaling enzymes and ion channels are physically associated with the actin cytoskeleton, raising the possibility that the subtle changes of the local actin cytoskeleton can, in turn, modulate the activities of these proteins. In this study, we reviewed the early and new experimental evidence supporting the notion of actin-regulated enzyme and ion channel activities in various cell types including the cells of immune response, neurons, oocytes, hepatocytes, and epithelial cells, with a special emphasis on the Ca2+ signaling pathway that depends on the synthesis of inositol 1,4,5-trisphosphate. Some of the features that are commonly found in diverse cells from a wide spectrum of the animal species suggest that fine-tuning of the activities of the enzymes and ion channels by the actin cytoskeleton may be an important strategy to inhibit or enhance the function of these signaling proteins.

Quantitative Analysis of the Cytoskeleton’s Role in Inward Rectifier KIR2.1 Forward and Backward Trafficking

“…1 . For example, Cytochalasin D has been shown to affect enzymes in the phospatidyl-4,5-biphosphate (PIP 2 ) metabolic pathways ( Vasilev et al, 2021 ). PIP 2 is an important factor for K IR 2.1 activity ( Huang et al, 1998 ).…”

STIM Proteins and Regulation of SOCE in ER-PM Junctions

“…A possible basis for the involvement of actin in SOCE could be plasma membrane PIP 2 interaction with, and modulation of, various actin-binding proteins (ABPs). An increase in plasma membrane PIP 2 levels induces actin filament assembly, while a reduction promotes disassembly [ 44 , 45 ]. These ABPs have been shown to associate with the plasma membrane via electrostatic interactions without penetrating the lipid bilayer or binding specifically to any regions of the plasma membrane [ 46 ].…”

“…As recently reviewed in [ 45 ], stimulation of immune cells leads to reorganization of the cortical actin cytoskeleton in order to transduce signals from the plasma membrane receptor to intracellular sites. Treatments with compounds that either promote actin depolymerization (e.g., lantrunculins A and B (Lat A and B respectively) and cytochalasin D (CytD) or stabilize the actin cytoskeletal network (e.g., jasplakinolide) have induced contrasting effects on SOCE in immune cells.…”

Temporal Modulation of Drug Desensitization Procedures

“…Challenging with the same antigen at a later time without eliciting an immune response is a hallmark of DS, however different antigens, including those that induce calcium fluxes needed for signaling will still elicit an allergenic response [12]. Such a feature implies that DS is antigenspecific and FcεRI-IgE complexes are still available for binding other antigens (epitope spreading) and for subsequent cross-linking [13]. The MC refractory state to allergens may be due to the internalization of FcεRI-IgE complexes through progressive cross-linking that corresponds to increasing antigen concentrations [14], which could potentially limit the pool of allergen sensors.…”