Ankyrin-Based Trafficking and Scaffolding of Membrane Proteins: Implications for Plasma Membrane Stability, Formation, and Specialization

Abstract

Through the collaborative actions of b-spectrin and ankyrin, a cytoskeletal adaptor protein, integral and peripheral membrane proteins find order and stability in the relatively fluid environment of the plasma membrane. Not only is the ankyrin/β-spectrin complex responsible for the proper targeting and retention of membrane proteins but it facilitates the formation of multi-protein complexes to maximize local signaling between membrane and effector proteins. Dysfunction in ankyrin or β-spectrin causes deficiencies in fundamental cellular properties such as membrane stability, excitability, and adhesion. This review focuses on the direct effects of ankyrin function on membrane proteins in terms of binding and stability, intracellular transport, membrane targeting and retention, and altered biophysical properties. We propose that ankyrin and β-spectrin are important for the normal progression of many membrane proteins along their biosynthetic pathway from stabilizing the membrane protein to it’s proper trafficking and eventual targeting and retention at membrane domains. The second half of the review addresses how an ankyrin/membrane protein interaction influences the local membrane environment with particular emphasis on membrane stability, membrane domain formation, and membrane domain specialization. We propose that not only are ankyrins necessary for erythroid membrane stability but they are required in some cells types for membrane domain formation and integral for the formation of specialized membrane domains in myocytes.