Roles of SLP-76, phosphoinositide 3-kinase, and gelsolin in the platelet shape changes initiated by the collagen receptor GPVI/FcRγ-chain complex

Author:

Falet Hervé1,Barkalow Kurt L.1,Pivniouk Vadim I.1,Barnes Michael J.1,Geha Raif S.1,Hartwig John H.1

Affiliation:

1. From the Division of Hematology, Brigham and Women's Hospital, and the Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA; and the Department of Biochemistry, Cambridge University, Cambridge, United Kingdom.

Abstract

How platelet shape change initiated by a collagen-related peptide (CRP) specific for the GPVI/FcRγ-chain complex (GPVI/FcRγ-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/FcRγ-chain and the roles of PI 3-kinase and gelsolin in lamellae spreading.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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