Montreal platelet syndrome: a defect in calcium-activated neutral proteinase (calpain).
Platelets from patients with Montreal platelet syndrome (MPS) consistently display a defect in the mechanisms that regulate platelet size during shape change and undergo spontaneous aggregation and stir-induced microaggregate formation. We now provide data that the surface glycoprotein composition of MPS platelets is indistinguishable from that of normal platelets. However, a defect in calcium-activated neutral proteinase (calpain) was detected in MPS platelets. The specific activity of calpain in the cytosolic fraction of platelets from four MPS patients was found to be only 30% of that in platelets from normal control donors (n = 18, P less than .001). Additionally, platelets from MPS patients (n = 3) contained only 50% (P less than .001) of the calpain I catalytic subunit antigen found in platelets from normal control donors (n = 9). Platelets from the asymptomatic father/grandfather of the MPS patients had normal amounts of both total calpain proteolytic activity and calpain I catalytic subunit antigen. This represents the first report of a defect in calpain in human cells. The abnormally low calpain activity in MPS platelets may account for the platelet defects characteristic of this disorder.
Okita
J R
JR
Blood Center of Southeastern Wisconsin, Milwaukee 53233.
Frojmovic
M M
MM
Kristopeit
S
S
Wong
T
T
Kunicki
T J
TJ
D001791:Blood Platelet Disorders / Q000097:blood* / Q000235:genetics; D001798:Blood Proteins / Q000032:analysis; D002154:Calpain / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D002384:Catalysis; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007123:Immunoelectrophoresis, Two-Dimensional; D007519:Isoantigens / Q000302:isolation & purification; D008297:Male; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000097:blood; D013347:Subcellular Fractions / Q000276:immunology; D013577:Syndrome
D001798:Blood Proteins; D007519:Isoantigens; D010980:Platelet Membrane Glycoproteins; D002154:Calpain