A mechanism of control of erythrocyte shape, differing significantly f
rom those previously proposed, is hypothesized. It was inferred from p
revious observations on the states of association of Band 3, the anion
exchange protein. Its salient points are as follows. (i) The membrane
skeleton is a pliable protein meshwork structure used to generate dif
ferent erythrocyte shapes. (ii) Band 3 is a dodecamer bound by one of
its subunits to ankyrin which is itself bound to the mid region of fil
amentous spectrin. (iii) Spectrin, by virtue of its high flexibility,
folds and unfolds and its folding links the two actin protofilaments b
ound at its ends to Band 3 through the intermediary of Band 4.1 and gl
ycophorin A. (iv) The alternate influx and efflux of anions mediated b
y Band 3 respectively fords and unfolds spectrin. (v) The ratio of Ban
d 3 molecules with outward-facing conformation to those with inward-fa
cing conformation controls the extents of folding of the skeleton spec
trin molecules. This ratio is governed by the Gibbs-Donnan equilibrium
ratio of anions and protons and by the Band 3 anion affinities and ex
change rates.