Increased membrane protein phosphorylation and anion transport activity in chorea-acanthocytosis.
OBJECTIVE
Chorea-acanthocytosis is a disorder characterized by neuronal degeneration and the presence of acanthocytic erythrocytes on blood smear. The abnormal function and structure of the membrane protein band 3 are considered to be of pathogenetic relevance in determining the erythrocyte defect.


METHODS
In a clinically evident case of chorea-acanthocytosis, the following parameters were investigated: membrane cholesterol and fatty acid composition, sulphate influx (as a measure of the anion transport activity), membrane protein phosphorylation, membrane casein and tyrosin-kinase activities; moreover, the promoter and all exons of the EPB3 gene were screened for possible mutations by single strand conformational polymorphism (SSCP) study.


RESULTS
The sulphate influx, the Ser/Thr phosphorylation level, and the membrane casein-kinase activity were increased in chorea-acanthocytosis compared with normal controls. In the intact vanadate-treated 32P-labelled erythrocytes, Tyr-phosphorylation of the cytoplasmic domain of band 3, as well as the poly(Glu, Tyr) kinase activity in the membranes, were enhanced in the patient's sample. Apparent molecular weight and concentration of band 3 on SDS/PAGE analysis, membrane fatty acid composition and cholesterol/phospholipid molar ratio were normal and the SSCP study of EPB3 exons did not show any abnormal polymorphisms.


CONCLUSIONS
An abnormal degree of phosphorylation of membrane proteins, in particular of band 2 (beta-subunit) and band 3, may contribute in determining both change of cell shape and increased anion transport in chorea-acanthocytosis.
Olivieri
O
O
Istituto di Patologia Medica, University of Verona, Italy.
De Franceschi
L
L
Bordin
L
L
Manfredi
M
M
Miraglia del Giudice
E
E
Perrotta
S
S
De Vivo
M
M
Guarini
P
P
Corrocher
R
R
D000050:Acanthocytes / Q000473:pathology*; D000328:Adult; D000838:Anions; D002819:Chorea / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006402:Hematologic Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017136:Ion Transport; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation
D000838:Anions; D008565:Membrane Proteins