Megakaryocytes assemble podosomes that degrade matrix and protrude through basement membrane

Schachtner, H. et al. (2013) Megakaryocytes assemble podosomes that degrade matrix and protrude through basement membrane. Blood, 121(13), pp. 2542-2552. (doi:10.1182/blood-2012-07-443457)

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Publisher's URL: http://dx.doi.org/10.1182/blood-2012-07-443457

Abstract

Megakaryocytes give rise to platelets via extension of proplatelet arms, which are released through the vascular sinusoids into the bloodstream. Megakaryocytes and their precursors undergo varying interactions with the extracellular environment in the bone marrow during their maturation and positioning in the vascular niche. We demonstrate that podosomes are abundant in primary murine megakaryocytes adherent on multiple extracellular matrix substrates, including native basement membrane. Megakaryocyte podosome lifetime and density, but not podosome size are dependent on the type of matrix, with podosome lifetime dramatically increased on collagen fibres compared with fibrinogen. Podosome stability and dynamics depend on actin cytoskeletal dynamics but not matrix metalloproteases. However, podosomes degrade matrix and appear to be important for megakaryocytes to extend protrusions across a native basement membrane. We thus demonstrate for the first time a fundamental requirement for podosomes in megakaryocyte process extension across a basement membrane and our results suggest that podosomes may have a role in proplatelet arm extension or penetration of basement membrane.

Item Type:Articles (Other)
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Machesky, Professor Laura and Sinclair, Miss Amy and Calaminus, Dr Simon and Michie, Dr Alison and Holyoake, Professor Tessa and Vukovic, Ms Milica
Authors: Schachtner, H., Calaminus, S. D. J., Sinclair, A., Monypenny, J., Blundell, M. P., Leon, C., Holyoake, T. L., Thrasher, A. J., Michie, A. M., Vukovic, M., Gachet, C., Jones, G. E., Thomas, S. G., Watson, S. P., and Machesky, L. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Blood
Publisher:American Society of Hematology
ISSN:0006-4971
ISSN (Online):1528-0020
Published Online:10 January 2013
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
533601The role of podosomes and lamellipodia in megakaryocyte function.Laura MacheskyBritish Heart Foundation (BHF)FS/09/034/27756ICS - BEATSON INSTITUTE FOR CANCER RES.
498551Key survival pathways in chronic myeloid leukaemic (CML) stem cells and novel approaches to their eradicationTessa HolyoakeCancer Research UK (CAN-RES-UK)11008RI CANCER SCIENCES