Alpha-adducin dissociates from F-actin and spectrin during platelet activation.
Aspectrin-based skeleton uniformly underlies and supports the plasma membrane of the resting platelet, but remodels and centralizes in the activated platelet. alpha-Adducin, a phosphoprotein that forms a ternary complex with F-actin and spectrin, is dephosphorylated and mostly bound to spectrin in the membrane skeleton of the resting platelet at sites where actin filaments attach to the ends of spectrin molecules. Platelets activated through protease-activated receptor 1, FcgammaRIIA, or by treatment with PMA phosphorylate adducin at Ser726. Phosphoadducin releases from the membrane skeleton concomitant with its dissociation from spectrin and actin. Inhibition of PKC blunts adducin phosphorylation and release from spectrin and actin, preventing the centralization of spectrin that normally follows cell activation. We conclude that adducin targets actin filament ends to spectrin to complete the assembly of the resting membrane skeleton. Dissociation of phosphoadducin releases spectrin from actin, facilitating centralization of spectrin, and leads to the exposure of barbed actin filament ends that may then participate in converting the resting platelet's disc shape into its active form.
Barkalow
Kurt L
KL
Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Italiano
Joseph E
JE
Chou
Denise E
DE
Matsuoka
Yoichiro
Y
Bennett
Vann
V
Hartwig
John H
JH
D000199:Actins / Q000378:metabolism*; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D044463:Receptor, PAR-1; D017452:Receptors, IgG / Q000187:drug effects / Q000378:metabolism; D018179:Receptors, Thrombin / Q000187:drug effects / Q000378:metabolism; D013049:Spectrin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000099291:Adducins
D000199:Actins; D015703:Antigens, CD; D002148:Calmodulin-Binding Proteins; D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; D011493:Protein Kinase C; D044463:Receptor, PAR-1; D017452:Receptors, IgG; D018179:Receptors, Thrombin; D013049:Spectrin; D013755:Tetradecanoylphorbol Acetate; D000099291:Adducins; C080568:Fc gamma receptor IIA