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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4066-4075.
Prepublished online as a Blood First Edition Paper on August 23, 2005; DOI 10.1182/blood-2005-06-2206.
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Submitted June 1, 2005
Accepted June 24, 2005
Mechanisms of organelle transport and capture along proplatelets during platelet production
Jennifer Richardson, Ramesh Shivdasani, Chad Boers, John Hartwig, and Joseph E Italiano Jr.*
Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
Dana Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA; Harvard School of Dental Medicine, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
* Corresponding author; email: jitaliano{at}rics.bwh.harvard.edu.
Megakaryocytes generate platelets by remodeling their cytoplasm into long proplatelet extensions, which serve as assembly lines for platelet production. Platelet packaging and release concludes at the tips of each proplatelet. Essential in this process is the distribution of organelles and platelet-specific granules into the nascent platelets. To investigate the mechanism of delivery of organelles into putative platelets, the distribution and dynamics of organelles/granules was monitored. Individual organelles are sent from the cell body to the proplatelets where they move bidirectionally until they are captured at proplatelet ends. Movement occurs at ~0.2 µm/min but pauses and changes in direction are frequent. At any given time, only ~30% of organelles/granules are in motion. Actin poisons do not diminish organelle motion and vesicular structures are intimately associated with the microtubules. Therefore, movement appears to involve microtubule-based forces. Bidirectional organelle movement is conveyed by the bipolar organization of microtubules within the proplatelet, as kinesin-coated beads move bidirectionally on the microtubule arrays of permeabilized proplatelets. Movement of organelles along proplatelets involves two mechanisms: organelles travel along microtubules, and the linked microtubules move relative to each other. These studies demonstrate that the components that form platelets are delivered to and assembled de novo along proplatelets.
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