REVIEWPlatelet α-granules: Basic biology and clinical correlates
Section snippets
Overview of platelet α-granules
Platelets 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 to 500 nm.1 They comprise roughly 10% of the platelet
Vesicle trafficking
The development of α-granules begins in the megakaryocyte, but continues in the circulating platelet. In the megakaryocyte, α-granules are derived in part from budding of small vesicles containing α-granule cargo from the trans-Golgi network (Fig. 1).[6], [7] In other cell models, an orchestrated assemblage of coat proteins (e.g., clathrin, COPII), adaptor proteins (e.g., AP-1, AP-2, AP-3), fusion machinery (e.g., soluble NSF attachment protein receptors [SNAREs]), and monomeric GTPases (e.g.,
Molecular mechanisms of α-granule release
α-Granule contents must be released from their intracellular repository in order to achieve their physiologic function. α-Granule contents are release when the α-granule membrane fuses with surface-connected membranes of the OCS or the plasma membrane.69 SNAREs represent the core of the fusion machinery. They are membrane-associated proteins that are oriented to the cytosol (Fig. 4). SNAREs associated with granules are termed vesicular SNAREs (vSNAREs), while those associated with target
Platelet α-granules content
α-Granule function derives from their contents. The content of α-granules includes both membrane bound proteins that become expressed on the platelet surface and soluble proteins that are released into the extracellular space. Most membrane bound proteins are also present on the resting plasma membrane92 These proteins include integrins (e.g., αIIb, α6, β3), immunoglobulin family receptors (e.g., GPVI, Fc receptors, PECAM), leucine-rich repeat family receptors (e.g., GPIb-IX-V complex),
Coagulation
Platelets secrete many mediators of blood coagulation. Whereas platelet dense granules contain high concentrations of low molecular weight compounds that potentiate platelet activation (e.g., ADP, serotonin, and calcium), α-granules concentrate large polypeptides that contribute to both primary and secondary hemostasis. α-Granules secrete fibrinogen and von Willebrand factor (vWf), adhesive proteins which mediate platelet–platelet and platelet–endothelial interactions. α-Granular vWf
Conflict of interest statement
The authors have no conflicts of interest to declare.
Acknowledgements
This work was supported by NIH HL87203 (R.F.) and T32 HL07917 (P.B.) and an Established Investigator Award from the American Heart Association (R.F.).
References (219)
- et al.
Platelet alpha-granules
Blood Rev
(1993) - et al.
Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released
Blood
(2008) - et al.
Evidence that differential packaging of the major platelet granule proteins von Willebrand factor and fibrinogen can support their differential release
J Thromb Haemost
(2007) - et al.
The human platelet membrane proteome reveals several new potential membrane proteins
Mol Cell Proteom
(2005) - et al.
Development of platelet secretory granules
Semin Cell Dev Biol
(2002) - et al.
Multivesicular bodies: co-ordinated progression to maturity
Curr Opin Cell Biol
(2008) - et al.
Multivesicular bodies are an intermediate stage in the formation of platelet alpha-granules
Blood
(1998) - et al.
Megakaryocyte dense granule components are sorted in multivesicular bodies
Blood
(2000) - et al.
Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules
Blood
(1999) - et al.
The Src family kinases, Fgr, Fyn, Lck, and Lyn, colocalize with coated membranes in platelets
Blood
(1997)