A variant of erythrocyte membrane skeletal protein band 4.1 associated with
hereditary elliptocytosis
M Garbarz, D Dhermy, MC Lecomte, C Feo, I Chaveroche, C Galand, O Bournier, O Bertrand and P Boivin
A family comprising three patients (a mother and two children) with mild
hereditary elliptocytosis was studied. Each patient had prominent
elliptocytosis, reduced red cell deformability, and normal erythrocyte
thermal sensitivity. Sodium dodecyl sulfate-polyacrylamide gel
electrophoresis (SDS-PAGE) of the erythrocyte membranes in each patient
showed decreased levels of band 4.1 (approximately half of the normal
value) and the presence of an additional band migrating below protein band
4.2. This additional band was shown to derive from protein 4.1. Comparative
partial proteolytic mapping of protein 4.1 and the additional band revealed
a number of common peptides. Enzyme-linked immunoelectrotransfer blots of
the patients' erythrocyte membranes using a monoclonal antibody to protein
4.1 revealed that, in addition to protein 4.1, two other bands below
protein 4.2 were stained; one of these bands migrated in the same position
as the additional band detected in the Coomassie Blue-stained gels.
Immunoblotting of the patients' whole cells using the antibody to protein
4.1 revealed that this altered band 4.1 occurred as such in the intact red
cell. SDS-PAGE of protein 4.1 purified from one patient showed the presence
of two lower molecular weight bands below protein 4.1; the lower band
migrated in the same position as the additional band found on SDS-PAGE of
the patients' erythrocyte membranes. The patient's purified protein 4.1
displayed a decrease of about 40% in the binding activity with crude
spectrin extracted from normal controls. Spectrin-spectrin interactions
were normal in the three patients. The additional band present in the
patients' red cell membranes probably represents a proteolytic degradation
product. This alteration, present both in whole cells and isolated
membranes, might affect the intact cells in vivo. We suggest that the
patients' erythrocyte membrane instability may be related to the presence
of an abnormal protein 4.1 whose modulatory influence on the spectrin-actin
interaction in the skeleton is defective.
Volume 64,
Issue 5,
pp. 1006-1015,
11/01/1984
Copyright © 1984 by The American Society of Hematology
