Spectrin assembly in avian erythroid development is determined by competing reactions of subunit homo- and hetero-oligomerization

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Abstract
Erythroid differentiation entails the biogenesis of a membrane skeleton, a network of proteins underlying and interacting with the plasma membrane1–3, whose major constituent is the heterodimeric protein spectrin, composed of two structurally similar but distinct subunits4, α (relative molecular mass (Mr) 240,000) and β (Mr 220,000), which interact side-on with each other to form a long rod-like molecule1,3,5–10. Interaction of this network with the membrane is mediated by the binding of the β subunit to ankyrin1,6,11–14, which in turn binds to the cytoplasmic domain of the transmembrane anion transporter (also referred to as band 3)1,15–19. Purified α and β subunits of spectrin from the membrane of mature red blood cells will spontaneously heterodimerize13,14,20–23, suggesting that assembly of the spectrinactin skeleton is a simple self-assembly process, but in vivo studies with developing chicken embryo erythroid cells have indicated that assembly in vivo is more complex24–29. We now present evidence that newly synthesized spectrin subunits in vivo or in vitro rapidly adopt one of two competing conformations, a heterodimer or a homo-oligomer. These competing reactions seem to determine the overall extent of spectrin assembled during erythroid development by determining which conformation will assemble onto the membrane-skeleton (the heterodimer) and which conformations are targeted for degradation (the homo-oligomers).