Spectrin self-association

In erythrocytes and most other cells, the major structural link of plasma membranes to the cytoskeleton is mediated by interactions between ankyrin and various integral membrane proteins, including Cf/HCOj antiporters, sodium ion pumps and voltage-dependent sodium ion channels. Ankyrin also binds to the =100 nm, rod-shaped, antiparallel a(3 heterodimers of spectrin and thus secures the cytoskeleton to the plasma membrane. Spectrin dimers self-associate to form tetramers and further to form a polygonal network parallel to the plasma membrane (Fig. 2-9D). Neurons contain both spectrin I, also termed erythroid spectrin, and spectrin II, also termed fodrin. Spectrin II is found throughout neurons, including axons, and binds to microtubules, whereas spectrin I occurs only in the soma and dendrites. 

Spectrin forms an integral part of the erythrocyte cytoskeletal architecture any defects that disrupt the association of the spectrin heterotetra-mer or the interaction with any of the other submembranous proteins can result in RBC defects (reviewed in Hassoun and Palek, 1996). Indeed, abnormalities of the /3-spectrin N-terminus and the a-spectrin G-terminus affect the self-association site and result in hereditary elliptocytosis and hereditary pyropoikilocytosis (Delaunay, 1995 Delaunay and Dhermy, 1993 Palek and Jarolim, 1993). 

The head of each spectrin chain interacts with the head of the complementary chain of another heterodimer. In the tetramer, there are paired interactions (Fig. 5-31), while in higher oligomers, a closed loop is formed, as the head region is quite flexible. This is shown for the hexamer in Fig. 5-39, but this self-association may continue indefinitely. 

The surface area of the red cell is approximately 140 p,m, which is greater than the surface of a sphere needed to enclose the contents of the red cell (98 p,m ). The presence of this extra membrane and the cytoskeleton that supports it allows the red cell to be stretched and deformed by mechanical stresses as the cell passes through narrow vascular beds. On the cytoplasmic side of the membrane, proteins form a two-dimensional lattice that gives the red cell its flexibility (Fig. 44.10). The major proteins are spectrin, actin, band 4.1, band 4.2, and ankyrin. Spectrin, the major protein, is a heterodimer composed of a and (3 subunits wound around each other. The dimers self-associate at the heads. At the opposite end of the spectrin dimers, actin and band 4.1 bind near to each other. Multiple spectrins can bind to each actin filament, resulting in a branched membrane cytoskeleton. 

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