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Title: Investigation of the functional and structural role of podosomes in megakaryocytes
Author: Schachtner, Hannah
ISNI:       0000 0004 2731 7649
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2013
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Megakaryocytes (Mks) give rise to platelets via extension of proplatelet arms, which are released through the vascular sinusoids into the bloodstream. Mks and their precursors undergo varying interactions with the extracellular environment in the bone marrow during their maturation and positioning in the vascular niche. The dynamic remodeling of the actin cytoskeleton and the formation of cell -matrix contacts such as podosomes are fundamental for this process. However, the role and function of podosome structures in Mks are poorly understood. Podsomes are well characterized in different cell-types of the myeloid lineage such as macrophages and dendritic cells. Their formation is associated with a dynamic F-actin turnover, fascilitated cell migration and the degradation of extracellular matrix (ECM). The function of podosome organelles is multifaceted and is described in association with cell adhesion, motility, ECM lysis, invasion and mechanosensors. A fundamental analysis of podosomes was necessary to define a potential function for these structures in Mks. I determined an abundant formation of classical podosomes with an F-actin core and a Vinculin ring in primary murine Mks, which were adherent on different physiological relevant ECM substrates such as fibrinogen, collagen I and a native basement membrane. Lifetime analysis was performed and was demonstrated to be dependent on the substrate as well as on Myosin-II activity. Another key feature of podosomes, the degradation of ECM proteins, could be detected and was mediated in an MMP associated manner. Furthermore, I verified that podosomes are necessary to penetrate a native basement membrane, which is amongst others part of blood vessels. II In this thesis I therefore demonstrate multifaceted properties of Mk podosomes and direct a potential function of these structures in the process of Mk maturation and possibly in platelet formation
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Q Science (General) ; R Medicine (General)