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Anatomy of the Platelet Cytoskeleton

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Platelets in Thrombotic and Non-Thrombotic Disorders

Abstract

The platelet cytoskeleton maintains the discoid shape of the resting platelet and mediates a rapid shape change in response to external stimuli at sites of vascular injury. At rest, specific cytoskeletal structures and molecules maintain the unique architecture of the platelet actin cytoskeleton, connect it to the plasma membrane, and prevent actin monomer assembly onto actin filaments. Platelet activation stimulates the interactions of cytoplasmic signals with actin regulatory proteins to initiate and amplify actin filament growth necessary for platelet shape change. This chapter reviews the cellular mechanisms and proteins maintaining the morphology of resting and activated platelets, focusing on the actin cytoskeleton and exciting recent mRNA and protein profiling studies, clinical observations, and mouse models.

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Acknowledgments

Supported by bridge grant awards from the Brigham Research Institute and the American Society of Hematology and National Institutes of Health, National Heart, Lung, and Blood Institute R01 grant HL126743. I thank Dr. John Hartwig for providing the electron microscopy image in Fig. 2.

Take-Home Messages

The platelet cytoskeleton: (1) maintains the discoid shape of the resting platelet and (2) mediates a rapid shape change in response to external stimuli at sites of vascular injury.

In resting platelets: (1) the spectrin-based membrane cytoskeleton and cytoplasmic actin filaments cross-linked by FlnA or bundled by α-actinins maintain the unique architecture of the platelet actin cytoskeleton and connect it to the plasma membrane and (2) actin monomer-sequestering proteins such as thymosin β4 and actin filament capping proteins such as CapZ prevent the assembly of actin monomers onto the barbed ends of the actin filaments composing the resting cytoskeleton.

In activated platelets: a rise in intracellular calcium and synthesis of membrane PIP2 stimulate the activities of actin regulatory proteins, such as gelsolin and the Arp2/3 complex, to initiate and amplify actin filament growth necessary for platelet shape change.

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  1. Division of Hematology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 02115, USA

    Hervé Falet Ph.D.

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  1. Hervé Falet Ph.D.
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Correspondence to Hervé Falet Ph.D. .

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  1. Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia , Perugia, Italy

    Paolo Gresele

  2. Houston Methodist Hospital , Houston, Texas, USA

    Neal S. Kleiman

  3. Bloodworks Northwest, University of Washington , Seattle, Washington, USA

    José A. Lopez

  4. Sackler Inst of Pulmonary Pharmacol, King’s College London, London, United Kingdom

    Clive P. Page

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Falet, H. (2017). Anatomy of the Platelet Cytoskeleton. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_11

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