Blood platelets are assembled principally at the ends of proplatelet processes produced by differentiated megakaryocytes

Megakaryocytes release mature platelets in a complex process. Platelets are known to be released from intermediate structures, designated proplatelets , which are long, tubelike extensions of the megakaryocyte cytoplasm. We ha ve resolved the ultrastructure of the megakaryocyte cytoskeleton at specifi c stages of proplatelet morphogenesis and correlated these structures with cytoplasmic remodeling events defined by video microscopy. Platelet product ion begins with the extension of large pseudopodia that use unique cortical bundles of microtubules to elongate and form thin proplatelet processes wi th bulbous ends; these contain a peripheral bundle of microtubules that loo ps upon itself and forms a teardrop-shaped structure. Contrary to prior obs ervations and assumptions, time-lapse microscopy reveals proplatelet proces ses to be extremely dynamic structures that interconvert reversibly between spread and tubular forms. Microtubule coils similar to those observed in b lood platelets are detected only at the ends of proplatelets and not within the platelet-sized beads found along the length of proplatelet extensions. Growth and extension of proplatelet processes is associated with repeated bending and bifurcation, which results in considerable amplification of fre e ends. These aspects are inhibited by cytochalasin B and, therefore, are d ependent on actin. We propose that mature platelets are assembled de novo a nd released only at the ends of proplatelets, and that the complex bending and branching observed during proplatelet morphogenesis represents an elega nt mechanism to increase the numbers of proplatelet ends.