Human platelet Galphaq deficiency is associated with decreased Galphaq gene expression in platelets but not neutrophils

• Published in: Thrombosis and haemostasis Vol. 87; no. 1; p. 129
• Main Authors: Gabbeta, J, Vaidyula, V R, Dhanasekaran, D N, Rao, A K
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2002
• Subjects: Blood Platelet Disorders - blood; Blood Platelet Disorders - genetics; Blood Platelets - metabolism; Calcium Signaling; Cell Lineage; DNA Mutational Analysis; DNA, Complementary - genetics; Female; Gene Expression Regulation; GTP-Binding Protein alpha Subunit, Gi2; GTP-Binding Protein alpha Subunits, Gi-Go - biosynthesis; GTP-Binding Protein alpha Subunits, Gq-G11; Hemorrhagic Disorders - blood; Hemorrhagic Disorders - genetics; Heterotrimeric GTP-Binding Proteins - biosynthesis; Heterotrimeric GTP-Binding Proteins - deficiency; Heterotrimeric GTP-Binding Proteins - genetics; Heterotrimeric GTP-Binding Proteins - physiology; Humans; Leukocyte Elastase - secretion; Middle Aged; Neutrophils - enzymology; Neutrophils - metabolism; Organ Specificity; Platelet Aggregation; Proto-Oncogene Proteins - biosynthesis; RNA, Messenger - biosynthesis; RNA, Messenger - blood; Transcription, Genetic
• ISSN: 0340-6245

G-proteins play an important role in platelet signal transduction and regulate responses upon activation of G-protein coupled receptors (GPCR). We have previously reported a patient with impaired platelet responses associated with deficiency in platelet Galphaq. To understand the molecular basis for this defect, the cDNA sequence encoding Galphaq (1080 bp) was obtained by reverse-transcription and polymerase chain reaction of platelet RNA; the cDNA sequence showed no mutations in the patient. Platelet Galphaq mRNA levels were decreased by >50% compared to normal subjects; platelet Galphai2 mRNA levels were normal. Neutrophil calcium mobilization and elastase secretion, upon activation with several agonists, and neutrophil Galphaq mRNA and protein levels were normal. These studies demonstrate that the patient has a defect in Galphaq gene expression in platelets but not neutrophils, possibly due to defects in transcriptional regulation or mRNA stability, and suggest a hematopoietic-lineage specific defect.