Biosynthesis and assembly of platelet GPIIb-IIIa in human megakaryocytes:
evidence that assembly between pro-GPIIb and GPIIIa is a prerequisite for
expression of the complex on the cell surface
A Duperray, A Troesch, R Berthier, E Chagnon, P Frachet, G Uzan and G Marguerie
DRF/Laboratoire d'Hematologie, INSERM U.217, Centre d'Etudes Nucleaires,
Grenoble, France.
The platelet membrane glycoproteins GPIIb and GPIIIa form a calcium-
dependent heterodimer that functions as a receptor for adhesive proteins on
stimulated platelets. In this study, we have investigated the kinetics of
the assembly reaction that result in GPIIb-IIIa dimerization. Pulse-chase
experiments analysis performed on human megakaryocytes obtained from liquid
cultures of chronic myelogenous leukemic patients with antibodies specific
for GPIIIa or GPIIb demonstrated the existence of a pro-GPIIb-GPIIIa
complex and of a large pool (60%) of unassociated GPIIIa; nearly all the
GPIIb and the pro- GPIIb molecules were found associated with GPIIIa. This
free GPIIIa was not exposed on the cell surface. Pulse-chase experiments on
a subclone of the human megakaryocytic cell line LAMA-84 revealed that the
cells from this subclone produced only the pro-GPIIb, which was neither
processed into mature GPIIb nor expressed on the cell surface. The
expression of GPIIIa in PMA treated cells resulted in the production of the
mature GPIIb form and the expression of the GPIIb-IIIa complex on the cell
surface. These results indicate that assembly between the early forms of
pro-GPIIb and GPIIIa is an obligatory step for the maturation of the
heterodimer and its expression on the cell surface.
Volume 74,
Issue 5,
pp. 1603-1611,
10/01/1989
Copyright © 1989 by The American Society of Hematology
