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Expression of a Functional N-Methyl-d-Aspartate–Type Glutamate Receptor by Bone Marrow Megakaryocytes

Authors :
Paul G. Genever
Ying Hong
Jorge D. Erusalimsky
David J.P. Wilkinson
Nicky M. Peet
Anthony Mathur
Timothy M. Skerry
Amanda J. Patton
Source :
Blood. 93:2876-2883
Publication Year :
1999
Publisher :
American Society of Hematology, 1999.

Abstract

Better understanding of hemostasis will be possible by the identification of new lineage-specific stimuli that regulate platelet formation. We describe a novel functional megakaryocyte receptor that belongs to a family of ionotropic glutamate receptors of theN-methyl-d-aspartate (NMDA) subtype responsible for synaptic neurotransmission in the central nervous system (CNS). Northern blotting and reverse-transcriptase polymerase chain reaction (RT-PCR) studies identified expression of NMDAR1 and NMDAR2D type subunit mRNA in rat marrow, human megakaryocytes, and MEG-01 clonal megakaryoblastic cells. Immunohistochemistry and in vivo autoradiographic binding of the NMDA receptor-specific antagonist MK-801 confirmed that megakaryocytes expressed open channel-forming NMDA receptors in vivo. Western blots indicated that megakaryocyte NMDAR1 was either unglycosylated or only glycosylated to low levels, and of identical size to CNS-type NMDAR1 after deglycosylation with endoglycosidase F/peptide-N-glycosidase F. In functional studies, we demonstrated that NMDA receptor activity was necessary for phorbol myristate acetate (PMA)-induced differentiation of megakaryoblastic cells; NMDA receptor blockade by specific antagonists significantly inhibited PMA-mediated increases in cell size, CD41 expression, and adhesion of MEG-01 cells. These results provide evidence for a novel pathway by which megakaryocytopoiesis and platelet production may be regulated.

Details

ISSN :
15280020 and 00064971
Volume :
93
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi...........165905cfe73ae9070e255bf6bd554c8e
Full Text :
https://doi.org/10.1182/blood.v93.9.2876