Multiple membrane extrusion sites drive megakaryocyte migration into bone marrow blood vessels

Brown, E., Carlin, L. M. , Nerlov, C., Lo Celso, C. and Poole, A. W. (2018) Multiple membrane extrusion sites drive megakaryocyte migration into bone marrow blood vessels. Life Science Alliance, 1(2), e201800061. (doi: 10.26508/lsa.201800061) (PMID:30393781) (PMCID:PMC6211653)

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Abstract

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.

Item Type:Articles
Additional Information:This work was supported by the British Heart Foundation (Programme grants RG/10/006/28299 and RG/15/16/31758) and the European Research Council (STG 337066). LM Carlin is supported by the Medical Research Council (grant MR/M01245X/1), the National Heart and Lung Institute Foundation, and Cancer Research UK. Intravital microscopy was in part performed at the Imperial College Facility for Imaging by Light Microscopy and in part supported by funding from the Wellcome Trust (grant P49828) and the Biotechnology and Biological Sciences Reseach Council (grant P48528).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Carlin, Dr Leo
Authors: Brown, E., Carlin, L. M., Nerlov, C., Lo Celso, C., and Poole, A. W.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Life Science Alliance
Publisher:Life Science Alliance
ISSN:2575-1077
ISSN (Online):2575-1077
Published Online:21 May 2018
Copyright Holders:Copyright © 2018 Brown et al.
First Published:First published in Life Science Alliance 1(2): e201800061
Publisher Policy:Reproduced under a Creative Commons License

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