Spectrin-adducin membrane skeleton: A missing link between epithelial junctions and the actin cytoskeletion?

Abstract

Adherens junctions (AJs) and tight junctions (TJs) represent key adhesive structures that regulate the apico-basal polarity and barrier properties of epithelial layers. AJs and TJs readily undergo disassembly and reassembly during normal tissue remodeling and disruption of epithelial barriers in diseases. Such junctional plasticity depends on the orchestrated dynamics of the plasma membrane with its underlying F-actin cytoskeleton, however the interplay between these cellular structures remains poorly understood. Recent studies highlighted the spectrin-adducin-based membrane skeleton as an emerging regulator of AJ and TJ integrity and remodeling. Here we discuss new evidences implicating adducin, spectrin and other membrane skeleton proteins in stabilization of epithelial junctions and regulation of junctional dynamics. Based on the known ability of the membrane skeleton to link cortical actin filaments to the plasma membrane, we hypothesize that the spectrin-adducin network serves as a critical signal and force transducer from the actomyosin cytoskeleton to junctions during remodeling of AJs and TJs.

Figure 1

Spectrin is recruited to contractile F-actin rings in calcium-depleted epithelial cells. Confluent T84 human intestinal epithelial cell monolayers and cells subjected to 60 min of calcium depletion were dual immunolabeled for αII -spectrin (green color) and F-actin (red color). Confocal microscopic images show that αII -spectin does not significantly colocalize with the perijunctional F-actin belt (arrows) in control cell monolayers. By contrast, αII-spectrin is enriched in contractile apical F-actin rings assembled in calcium-depleted epithelial cells (arrowheads). Scale bar, 5 µm.

Figure 2

Hypothetical mechanisms by which the membrane skeleton can mediate F-actin dependent disassembly of epithelial junctions. The scheme depicts two different models proposed to explain how the spectrin-adducin membrane skeleton can mediate epithelial AJ/TJ disassembly driven by perijunctional actomyosin contractility. Model A implies that the membrane skeleton physically links actin filaments to cytosolic plaques of AJs and TJs, whereas Model B proposes indirect force transduction via adducin-spectrin-mediated actin attachment to the plasma membrane in a close vicinity of apical junctions. See detailed explanation in the text.