Faculty Collaboration Database

Surface expression of glycoprotein ib alpha is dependent on glycoprotein ib beta: evidence from a novel mutation causing Bernard-Soulier syndrome. Blood 2000 Jul 15;96(2):532-9

Date

07/11/2000

Pubmed ID

10887115

DOI

10.1182/blood.v96.2.532.014k33_532_539

Scopus ID

2-s2.0-0034661909 (requires institutional sign-in at Scopus site)   58 Citations

Abstract

Bernard-Soulier syndrome is a rare bleeding disorder caused by a quantitative or qualitative defect in the platelet glycoprotein (GP) Ib-IX-V complex. The complex, which serves as a platelet receptor for von Willebrand factor, is composed of 4 subunits: GPIb alpha, GPIb beta, GPIX, and GPV. We here describe the molecular basis of a novel form of Bernard-Soulier syndrome in a patient in whom the components of the GPIb-IX-V complex were undetectable on the platelet surface. Although confocal imaging confirmed that GPIb alpha was not present on the platelet surface, GPIb alpha was readily detectable in the patient's platelets. Moreover, immunoprecipitation of plasma with specific monoclonal antibodies identified circulating, soluble GPIb alpha. DNA-sequence analysis revealed normal sequences for GPIb alpha and GPIX. There was a G to A substitution at position 159 of the gene encoding GPIb beta, resulting in a premature termination of translation at amino acid 21. Studies of transient coexpression of this mutant, W21stop-GPIb beta, together with wild-type GPIbalpha and GPIX, demonstrated a failure of GPIX expression on the surface of HEK 293T cells. Similar results were obtained with Chinese hamster ovary alpha IX cells, a stable cell line expressing GPIbalpha that retains the capacity to re-express GPIX. Thus, we found that GPIbbeta affects the surface expression of the GPIb-IX complex by failing to support the insertion of GPIb alpha and GPIX into the platelet membrane. (Blood. 2000;96:532-539)

Author List

Moran N, Morateck PA, Deering A, Ryan M, Montgomery RR, Fitzgerald DJ, Kenny D

Author

Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Monoclonal
Bernard-Soulier Syndrome
Blood Platelets
CHO Cells
Cell Membrane
Cricetinae
Gene Expression
Humans
Immunosorbent Techniques
In Situ Hybridization, Fluorescence
Male
Microscopy, Confocal
Middle Aged
Mutation
Platelet Glycoprotein GPIb-IX Complex
Sequence Analysis, DNA
Transfection