Roles of SLP-76, phosphoinositide 3-kinase, and gelsolin in the platelet shape changes initiated by the collagen receptor GPVI/FcR gamma-chain complex.
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)
Falet
H
H
Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Barkalow
K L
KL
Pivniouk
V I
VI
Barnes
M J
MJ
Geha
R S
RS
Hartwig
J H
JH
D008841:Actin Cytoskeleton / Q000187:drug effects; D000199:Actins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D020013:Calcium Signaling / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003094:Collagen / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018260:Gelsolin / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000494:pharmacology / Q000502:physiology*; D015539:Platelet Activation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D038981:Receptors, Collagen; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*; D018179:Receptors, Thrombin / Q000502:physiology; D015398:Signal Transduction
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018260:Gelsolin; D016023:Integrins; D010446:Peptide Fragments; D010750:Phosphoproteins; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; D017452:Receptors, IgG; D018179:Receptors, Thrombin; C092947:SLP-76 signal Transducing adaptor proteins; C098341:platelet membrane glycoprotein VI; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases