Platelet production by megakaryocytes: protoplatelet theory justifies cytoplasmic fragmentation model.

The maturation of megakaryocytes (MKs) leading to platelet production is carefully reviewed. For instance, when MK with ploidy 16N enters the maturation stage, eight centrosomes are clustered in the cell center surrounded by 16N nucleus. Each bundle of microtubules (MTs) emanated from the respective centrosome supports and organize eight equally volumed cytoplasmic compartments which together compose one single 16N MK. Then, the following three processes take place in parallel until the complete maturation of MKs Virchow's Arch. 1906;186:55-63. Two centrioles, composing centrosome, are separated and each one with pericentriolar material migrates to just beneath the plasma membrane through the MT bundle [corresponding to a half of the interphase array, originated from one centrosome, supporting one "putative cytoplasmic compartment "(PCC)] (Blood. 2005;106:4066-75). Platelet specific granules and other cellular components, newly formed in the central field of the cell, are transported along the MTs and many platelet territories, future platelets, are elaborated as a tandem array from the center to periphery in each PCC [3]. All the important membranes including plasma membrane and platelet demarcation membrane (DM) are synthesized de novo and those are transported as membrane vesicles (MVs) from Golgi body along the MTs. MVs arranged on the boundary surface between neighboring PCCs undergo fusion and fission to yield a paired membrane. Further connection with the external milieu results in the completion of DM system. The PCC covered by a sheet of DM is designated as protoplatelet. Excessive production of the MVs, most probably intervenes between the respective protoplatelets. Eventually, the matured MK ruptures as a whole, resulting in release of platelets from protoplatelets and many of MVs, though the mechanism is not fully elucidated yet.