Multiple membrane extrusion sites drive megakaryocyte migration into bone marrow blood vessels
2018
Platelets, cells central to hemostasis and thrombosis, are formed from parent
cell megakaryocytes. Although the process is highly efficient in vivo, our
ability to generate them in vitro is still remarkably inefficient. We proposed
that greater understanding of the process in vivo is needed and used an imaging
approach, intravital correlative light electron microscopy, to visualize
platelet generation in bone marrow in the living mouse. In contrast to current
understanding, we found that most megakaryocytes enter the sinusoidal space as
large protrusions rather than extruding fine proplatelet extensions. The
mechanism for large protrusion migration also differed from that of proplatelet
extension. In vitro, proplatelets extend by sliding of dense bundles of
microtubules, whereas in vivo our data showed the absence of microtubule bundles
in the large protrusion, but the presence of multiple fusion points between the
internal membrane and the plasma membrane, at the leading edge of the protruding
cell. Mass membrane fusion, therefore, drives megakaryocyte large protrusions
into the sinusoid, significantly revising our understanding of the fundamental
biology of platelet formation in vivo.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
30
References
19
Citations
NaN
KQI