Megakaryocytes assemble podosomes that degrade matrix and protrude through basement membrane

Schachtner, Hannah; Calaminus, Simon D. J.; Sinclair, Amy; Monypenny, James; Blundell, Michael P.; Leon, Catherine; Holyoake, Tessa L.; Thrasher, Adrian J.; Michie, Alison M.; Vukovic, Milica; Gachet, Christian; Jones, Gareth E.; Thomas, Steven G.; Watson, Steve P.; Machesky, Laura M.

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 fibers 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.

Citation

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., & Machesky, L. M. (2013). Megakaryocytes assemble podosomes that degrade matrix and protrude through basement membrane. Blood, 121(13), 2542-2552. https://doi.org/10.1182/blood-2012-07-443457

• Journal Article Type: Article
• Acceptance Date: Dec 21, 2012
• Online Publication Date: Mar 28, 2013
• Publication Date: Mar 28, 2013
• Deposit Date: Nov 13, 2014
• Journal: Blood
• Print ISSN: 0006-4971
• Publisher: American Society of Hematology
• Peer Reviewed: Peer Reviewed
• Volume: 121
• Issue: 13
• Pages: 2542-2552
• DOI: https://doi.org/10.1182/blood-2012-07-443457
• Keywords: Immunology; Cell Biology; Biochemistry; Hematology
• Public URL: https://hull-repository.worktribe.com/output/469379
• Publisher URL: http://bloodjournal.hematologylibrary.org/content/121/13/2542.full.html
• Contract Date: Nov 13, 2014