Spectrin-based skeleton as an actor in cell signaling

Abstract

This review focuses on the recent advances in functions of spectrins in non-erythroid cells. We discuss new data concerning the commonly known role of the spectrin-based skeleton in control of membrane organization, stability and shape, and tethering protein mosaics to the cellular motors and to all major filament systems. Particular effort has been undertaken to highlight recent advances linking spectrin to cell signaling phenomena and its participation in signal transduction pathways in many cell types.

Fig. 1

A model of the human red cell membrane. The spectrin-actin interaction is modulated by accessory proteins such as protein 4.1, together with dematin, adducin, tropomyosin and tropomodulin. Their functions are to stabilize the actin-spectrin complex, to maintain actin filament length (adducin acts as a capping protein), and to bind the spectrin-based network to the transmembrane proteins (the glycophorin C, the anion exchanger AE1) via adapter proteins (protein p55 and protein 4.2). Another major binding site to membrane is mediated via ankyrin, which binds to β-spectrin and the anion exchanger AE1. The Rh/RhAG-ankyrin complex can be also a link between the red cell membrane and the spectrin-based skeleton. Spectrins also interact directly with phospholipids such as phosphatidylserine and phosphatidylethanolamine, membrane components actively confined to the inner leaflet of the lipid bilayer. The aminophospholipid-binding sites in β-spectrin are localized in close proximity to the attachment sites for both ankyrin and 4.1, the proteins engaged in spectrin links to the membrane. AE1 anion exchanger, GPA glycophorin A, GPB glycophorin B, GPC glycophorin C, GLUT 1 glucose transporter 1, Rh rhesus factor, RhAG Rh-associated glycoprotein