Platelet α-granules: Basic biology and clinical correlates

Abstract

Summaryα-Granules are essential to normal platelet activity. These unusual secretory granules derive their cargo from both regulated secretory and endocytotic pathways in megakaryocytes. Rare, inheritable defects of α-granule formation in mice and man have enabled identification of proteins that mediate cargo trafficking and α-granule formation. In platelets, α-granules fuse with the plasma membrane upon activation, releasing their cargo and increasing platelet surface area. The mechanisms that control α-granule membrane fusion have begun to be elucidated at the molecular level. SNAREs and SNARE accessory proteins that control α-granule secretion have been identified. Proteomic studies demonstrate that hundreds of bioactive proteins are released from α-granules. This breadth of proteins implies a versatile functionality. While initially known primarily for their participation in thrombosis and hemostasis, the role of α-granules in inflammation, atherosclerosis, antimicrobial host defense, wound healing, angiogenesis, and malignancy has become increasingly appreciated as the function of platelets in the pathophysiology of these processes has been defined. This review will consider the formation, release, and physiologic roles of α-granules with special emphasis on work performed over the last decade. Keywordsα-granule; vesicle trafficking; endocytosis; secretion; hemostasis Overview of platelet α-granulesPlatelets are anucleate, discoid shaped blood cells that serve a critical function in hemostasis and other aspects of host defense. These cells are replete with secretory granules, which are critical to normal platelet function. Among the three types of platelet secretory granules -α-granules, dense granules, and lysosomes -the α-granule is the most abundant. There are approximately 50-80 α-granules per platelet, ranging in size from 200-500 nm. 1 They comprise roughly 10% of the platelet volume, 10-fold more than dense granules. The total α-granule membrane surface area per platelet is 14 μm 2 , ~8-fold more than dense granules and approximately equal to that of the open canalicular system (OCS), 1 an elaborate system of tunneling invaginations of the cell membrane unique to the platelet. 2 The extra membrane *Address correspondence to: Robert Flaumenhaft, M.D., Ph.D., Center for Life Science, Rm 939, Beth Israel Deaconess Medical Center, 3 Blackfan Circle, Boston, MA, 02215. Tel: 617-735-4005, Fax: 617-735-4000, Email: E-mail: rflaumen@bidmc.harvard.edu. Conflict of interest statementThe authors have no conflicts of interest to declare.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the jour...

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