Multiple membrane extrusion sites drive megakaryocyte migration into bone marrow blood vessels: Megakaryocytes migrate by membrane extrusion

Edward Brown, Leo M. Carlin, Claus Nerlov, Christina Lo Celso, Alastair Poole

Research output: Contribution to journalArticle (Academic Journal)peer-review

16 Citations (Scopus)
173 Downloads (Pure)

Abstract

Platelets, cells central to hemostasis and thrombosis, are formed from parent cell megakaryocytes. Whilst 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 an 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.
Original languageEnglish
Article numbere201800061
Number of pages12
JournalLife Science Alliance
Volume1
Issue number2
Early online date21 May 2018
DOIs
Publication statusPublished - May 2018

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