Abstract
How platelet shape change initiated by a collagen-related peptide (CRP) specific for the GPVI/FcR gamma-chain complex (GPVI/FcR gamma-chain) is coupled to SLP-76, phosphoinositide (PI) 3-kinase, and gelsolin is reported. As shown by video microscopy, platelets rapidly round and grow dynamic filopodial projections that rotate around the periphery of the cell after they contact a CRP-coated surface. Lamellae subsequently spread between the projections. All the actin-driven shape changes require SLP-76 expression. SLP-76 is essential for the Ca(++) mobilization induced by CRP, whereas PI 3-kinase only modulates it. The extension of lamellae requires net actin assembly and an exposure of actin filament barbed ends downstream of PI 3-kinase. Gelsolin expression is also required for the extension of lamellae, but not for the formation of filopodia. Altogether, the data describe the role of SLP-76 in the platelet activation initiated by GPVI/FcR gamma-chain and the roles of PI 3-kinase and gelsolin in lamellae spreading. (Blood. 2000;96:3786-3792)
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin Cytoskeleton / drug effects
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Actins / drug effects
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Actins / metabolism
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Actins / physiology
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Adaptor Proteins, Signal Transducing
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Animals
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Blood Platelets / cytology
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Blood Platelets / drug effects*
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Blood Platelets / ultrastructure
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Calcium Signaling / drug effects
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Cell Size / drug effects
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Collagen / chemistry
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Collagen / metabolism
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Collagen / pharmacology
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Gelsolin / pharmacology
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Gelsolin / physiology*
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Humans
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Integrins / metabolism
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Integrins / physiology
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Mice
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Mice, Mutant Strains
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphatidylinositol 3-Kinases / physiology*
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Phosphoproteins / pharmacology
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Phosphoproteins / physiology*
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Platelet Activation / drug effects
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Platelet Membrane Glycoproteins / metabolism
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Platelet Membrane Glycoproteins / physiology*
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Receptors, Collagen
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Receptors, IgG / metabolism
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Receptors, IgG / physiology*
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Receptors, Thrombin / physiology
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Signal Transduction
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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Gelsolin
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Integrins
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Peptide Fragments
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Phosphoproteins
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Platelet Membrane Glycoproteins
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Receptors, Collagen
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Receptors, IgG
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Receptors, Thrombin
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SLP-76 signal Transducing adaptor proteins
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platelet membrane glycoprotein VI
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Collagen
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Phosphatidylinositol 3-Kinases