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 have resolved the ultrastructure of the megakaryocyte cytoskeleton at specific stages of proplatelet morphogenesis and correlated these structures with cytoplasmic remodeling events defined by video microscopy. Platelet production begins with the extension of large pseudopodia that use unique cortical bundles of microtubules to elongate and form thin proplatelet processes with bulbous ends; these contain a peripheral bundle of microtubules that loops upon itself and forms a teardrop-shaped structure. Contrary to prior observations and assumptions, time-lapse microscopy reveals proplatelet processes to be extremely dynamic structures that interconvert reversibly between spread and tubular forms. Microtubule coils similar to those observed in blood 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 free ends. These aspects are inhibited by cytochalasin B and, therefore, are dependent on actin. We propose that mature platelets are assembled de novo and released only at the ends of proplatelets, and that the complex bending and branching observed during proplatelet morphogenesis represents an elegant mechanism to increase the numbers of proplatelet ends.
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13 December 1999
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December 13 1999
Blood Platelets Are Assembled Principally at the Ends of Proplatelet Processes Produced by Differentiated Megakaryocytes
Joseph E. Italiano, Jr.,
Joseph E. Italiano, Jr.
aDivision of Hematology, Brigham and Women's Hospital, Boston, Massachusetts 02115
bDepartment of Medicine, Harvard Medical School, Boston, MA 02115
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Patrick Lecine,
Patrick Lecine
bDepartment of Medicine, Harvard Medical School, Boston, MA 02115
cDepartment of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115
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Ramesh A. Shivdasani,
Ramesh A. Shivdasani
bDepartment of Medicine, Harvard Medical School, Boston, MA 02115
cDepartment of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115
dDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115
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John H. Hartwig
John H. Hartwig
aDivision of Hematology, Brigham and Women's Hospital, Boston, Massachusetts 02115
bDepartment of Medicine, Harvard Medical School, Boston, MA 02115
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Joseph E. Italiano, Jr.
aDivision of Hematology, Brigham and Women's Hospital, Boston, Massachusetts 02115
bDepartment of Medicine, Harvard Medical School, Boston, MA 02115
Patrick Lecine
bDepartment of Medicine, Harvard Medical School, Boston, MA 02115
cDepartment of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115
Ramesh A. Shivdasani
bDepartment of Medicine, Harvard Medical School, Boston, MA 02115
cDepartment of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115
dDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115
John H. Hartwig
aDivision of Hematology, Brigham and Women's Hospital, Boston, Massachusetts 02115
bDepartment of Medicine, Harvard Medical School, Boston, MA 02115
The online version of this article contains supplemental material.
Received:
September 09 1999
Revision Requested:
October 29 1999
Accepted:
November 02 1999
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Cell Biol (1999) 147 (6): 1299–1312.
Article history
Received:
September 09 1999
Revision Requested:
October 29 1999
Accepted:
November 02 1999
Citation
Joseph E. Italiano, Patrick Lecine, Ramesh A. Shivdasani, John H. Hartwig; Blood Platelets Are Assembled Principally at the Ends of Proplatelet Processes Produced by Differentiated Megakaryocytes. J Cell Biol 13 December 1999; 147 (6): 1299–1312. doi: https://doi.org/10.1083/jcb.147.6.1299
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