Immunological analogues of band 3, the
anion transporter, have been identified in all cells that have been studied, including both isolated neurons and neurons of the central nervous system. We studied band 3 structural/functional relationships in a family in which the proposita has a serious, progressive, genetic
neurologic disorder with
acanthocytosis (
choreoacanthocytosis). Biochemical studies of erythrocytes from the proposita, her mother and brother revealed that maximal
sulfate transport velocity (Vmax) and
sodium transport were increased,
glucose efflux was decreased.
Ankyrin binding was normal. Immunologic studies revealed increased
IgG binding to middle-aged cells of the proposita and her brother, binding of
antibodies to aged band 3 to a distinct region of band 3 in erythrocyte membranes in immunoblots, and binding of
choreoacanthocytosis sera
IgG to erythroid and brain band 3 and synthetic
peptides of band 3 in immunoblots.
Antibodies to neural and, to a lesser extent, renal tissue were observed in
choreoacanthocytosis sera. These
antibodies appear to have a band 3 specificity.
Monoclonal antibodies to 150 residues of the carboxyl terminus of band 3 stained two band 3 fragments in immunoblots of
chymotrypsin-digested membranes that are not present in control cells. This suggests that band 3 is altered in this autosomal recessive
neurologic disorder. In addition, these
monoclonal antibodies stained five band 3 breakdown products in membranes of untreated red cells in both control and
choreoacanthocytosis cells. The possibility that a disturbance of some function of band 3 may contribute to the neurologic abnormalities in affected individuals is intriguing. This is the first evidence for abnormalities of membrane transport in the
neurologic disorder known as
choreoacanthocytosis.