Molecular basis of platelet granule secretion.
The energy-dependent release of granule contents from activated platelets is a well-established component of normal hemostasis and thrombosis. A role for membrane fusion in this process has been presumed for decades, but only recently have the mechanisms of platelet membrane fusion been investigated at the molecular level. Such studies have demonstrated that platelet membrane fusion is controlled by lipid components of the membrane bilayer, by transmembrane proteins termed SNARE proteins, and by chaperone proteins that interact with SNARE proteins. This core membrane fusion machinery is controlled by activation-dependent changes in cytoskeletal organization, intracellular calcium levels, kinase activity, and intracellular protease activity. Through these mechanisms, interactions of ligands with their cognate cell-surface receptors are transmitted to the membrane fusion machinery to facilitate membrane fusion and secretion of granule contents from platelets.
Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass 02115, USA. rflaumen@bidmc.harvard.edu
Robert
R
Flaumenhaft
D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D003594:Cytoplasmic Granules / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology; D010450:Endopeptidases / Q000502:physiology; D008561:Membrane Fusion / Q000502:physiology*; D008563:Membrane Lipids / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology; D010712:Phosphatidic Acids / Q000494:pharmacology / Q000502:physiology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000494:pharmacology / Q000502:physiology; D015539:Platelet Activation / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins
D008563:Membrane Lipids; D008565:Membrane Proteins; D018832:Molecular Chaperones; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D011493:Protein Kinase C; D010450:Endopeptidases; D002118:Calcium