Mechanisms of cold-induced platelet actin assembly. J Biol Chem 2001 Jul 06;276(27):24751-9
Date
05/01/2001Pubmed ID
11328807DOI
10.1074/jbc.M011642200Scopus ID
2-s2.0-0035816637 (requires institutional sign-in at Scopus site) 84 CitationsAbstract
Various agonists but also chilling cause blood platelets to increase cytosolic calcium, polymerize actin, and change shape. We report that cold increases barbed end nucleation sites in octyl glucoside-permeabilized platelets by 3-fold, enabling analysis of the intermediates of this response. Although chilling does not change polyphosphoinositide (ppI) levels, a ppI-binding peptide completely inhibits cold-induced nucleation. The C terminus of N-WASp, which inhibits the Arp2/3 complex, blocks nucleation by 40%; GDPbetaS, N17Rac and N17Cdc42 have no effects. Some gelsolin translocates to the detergent-insoluble cytoskeleton after cooling. Chilled platelets from gelsolin-deficient mice have approximately 50% fewer new actin nuclei compared with platelets from wild-type mice. EGTA completely inhibits gelsolin translocation into the cytoskeleton, and the small amount of gelsolin initially there becomes soluble. Chilling releases adducin from the detergent-resistant cytoskeleton. We conclude that platelet actin filament assembly induced by cooling involves ppI-mediated actin filament barbed end uncapping and de novo nucleation independently of surface receptors or downstream signaling intermediates besides calcium. The actin-related changes occur in platelets at temperatures below 37 degrees C, suggesting that the platelet may be more activable at temperatures at the body surface than at core temperature, thereby favoring superficial hemostasis over internal thrombosis.
Author List
Hoffmeister KM, Falet H, Toker A, Barkalow KL, Stossel TP, Hartwig JHAuthors
Herve Falet PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinKarin Hoffmeister MD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Actin-Related Protein 2Actin-Related Protein 3
Actins
Animals
Blood Platelets
Cold Temperature
Cytoskeletal Proteins
GTP Phosphohydrolases
Gelsolin
Glucosides
Guanosine Diphosphate
Hemostasis
Humans
Mice
Nerve Tissue Proteins
Phosphatidylinositol Phosphates
Polymers
Rabbits
Thionucleotides
Wiskott-Aldrich Syndrome Protein, Neuronal