Restoration of responsiveness of phospholipase Cγ2-deficient platelets by enforced expression of phospholipase Cγ1

PloS One
Yongwei ZhengDebra K Newman

Abstract

Receptor-mediated platelet activation requires phospholipase C (PLC) activity to elevate intracellular calcium and induce actin cytoskeleton reorganization. PLCs are classified into structurally distinct β, γ, δ, ε, ζ, and η isoforms. There are two PLCγ isoforms (PLCγ1, PLCγ2), which are critical for activation by tyrosine kinase-dependent receptors. Platelets express both PLCγ1 and PLCγ2. Although PLCγ2 has been shown to play a dominant role in platelet activation, the extent to which PLCγ1 contributes has not been evaluated. To ascertain the relative contributions of PLCγ1 and PLCγ2 to platelet activation, we generated conditionally PLCγ1-deficient, wild-type (WT), PLCγ2-deficient, and PLCγ1/PLCγ2 double-deficient mice and measured the ability of platelets to respond to different agonists. We found that PLCγ2 deficiency abrogated αIIbβ3-dependent platelet spreading, GPVI-dependent platelet aggregation, and thrombus formation on collagen-coated surfaces under shear conditions, which is dependent on both GPVI and αIIbβ3. Addition of exogenous ADP overcame defective spreading of PLCγ2-deficient platelets on immobilized fibrinogen, suggesting that PLCγ2 is required for granule secretion in response to αIIbβ3 ligation. Consistentl...Continue Reading

References

Jun 1, 1984·The Journal of Cell Biology·J E FoxD R Phillips
Mar 1, 1993·Blood Reviews·P Harrison, E M Cramer
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·Q S JiG Carpenter
Jun 13, 1997·The Journal of Biological Chemistry·S G Rhee, Y S Bae
Jun 9, 1998·Cellular Signalling·C Keenan, D Kelleher
Oct 30, 1998·Cellular Signalling·W S Liu, C A Heckman
May 24, 2000·Cellular and Molecular Life Sciences : CMLS·M D BootmanP Lipp
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A HashimotoT Kurosaki
Jun 8, 2001·Annual Review of Biochemistry·S G Rhee
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·M J BerridgeM D Bootman
Jul 2, 2003·The Journal of Biological Chemistry·Peter WonerowSteve P Watson
Jun 19, 2004·Blood·Sanford J Shattil, Peter J Newman
Aug 26, 2004·FEBS Letters·Vipul RathorePeter J Newman
Mar 19, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Christelle NonneFrançois Lanza
Jul 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ilaria TassiMarco Colonna
Oct 29, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Imke C A MunnixJohan W M Heemskerk
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeyarani RegunathanSubramaniam Malarkannan
Oct 24, 2006·Thrombosis Research·Katsue Suzuki-InoueYukio Ozaki
Oct 24, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alessandra WarrenPatrick Bertolino
Mar 6, 2007·Advances in Enzyme Regulation·Jang Hyun ChoiPann-Ghill Suh
Oct 13, 2007·The Journal of Clinical Investigation·Daniel B GrahamWojciech Swat
Jul 3, 2008·BMB Reports·Pann-Ghill SuhSung Ho Ryu
Jan 13, 2009·The Journal of Biological Chemistry·Shengli XuKong-Peng Lam
Feb 4, 2010·The Journal of Experimental Medicine·Guoping FuRenren Wen
Sep 28, 2010·Trends in Biochemical Sciences·Tom D Bunney, Matilda Katan
Nov 13, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Zhenyu LiXiaoping Du
Jan 26, 2011·Journal of Thrombosis and Haemostasis : JTH·A EcklyC Gachet
May 21, 2011·Blood·Jesse W RowleyAndrew S Weyrich
Jul 28, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guoping FuRenren Wen
Aug 8, 2013·Current Opinion in Hematology·Wolfgang Bergmeier, Lucia Stefanini

❮ Previous
Next ❯

Citations

Nov 23, 2016·Biomolecules & Therapeutics·Eun-Kyung ShinJin-Ho Chung
Feb 24, 2018·Scientific Reports·Harvey G RowethGavin E Jarvis
Jun 6, 2019·International Journal of Molecular Sciences·Chih-Wei HsiaJoen-Rong Sheu
Apr 24, 2018·The Journal of Clinical Investigation·Valerie B O'DonnellMichael Jo Wakelam
Nov 13, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Beom Soo KimScott J Cameron

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
electrophoresis
ELISA
flow cytometry

Software Mentioned

Graphpad Prism
MetaMorph

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.

Advanced Imaging of Cellular Signaling

Cell signaling is a vital mechanism for communication within cells and outside with the environment. Several different signaling pathways have been found and advanced imaging techniques are being developed to visualize the molecules involved in these signaling pathways. Find the latest research in advanced imaging of cellular signaling here.

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.