New explanations for old observations: Marginal band coiling during platelet activation

Abstract

Summary: Blood platelets are tiny cell fragments derived from megakaryocytes. Their primary function is to control blood vessel integrity and ensure hemostasis if a vessel wall is damaged. Circulating quiescent platelets have a flat, discoid shape maintained by a circumferential microtubule bundle, called the marginal band (MB). In the case of injury platelets are activated and rapidly adopt a spherical shape due to microtubule motor-induced elongation and subsequent coiling of the MB. Platelet activation and shape change can be transient or become irreversible. This depends on the strength of the activation stimulus, which is translated into a cytoskeletal crosstalk between microtubules, their motors and the actomyosin cortex, ensuring stimulus-response coupling. Following microtubule motor-driven disc-to-sphere transition, a strong stimulus will lead to compression of the sphere through actomyosin cortex contraction. This will concentrate the granules in the center of the platelet and accelerate their exocytosis. Once granules are released, platelets have crossed the point of no return to irreversible activation. This review summarizes the current knowledge of the molecular mechanism leading to platelet shape change, with a special emphasis on microtubules, and refers to previously published observations, which have been essential for generating an integrated view of cytoskeletal rearrangements during platelet activation.