Investigation of the functional and structural role of podosomes in megakaryocytes

Schachtner, Hannah (2013) Investigation of the functional and structural role of podosomes in megakaryocytes. PhD thesis, University of Glasgow.

Abstract

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

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: podosomes, cell adhesion, cell migration, megakaryocytes
• Subjects: Q Science > Q Science (General); R Medicine > R Medicine (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences > Beatson Institute of Cancer Research
• Supervisor's Name: Machesky, Dr. L.M.
• Date of Award: 2013
• Depositing User: Dr. HS Schachtner
• Unique ID: glathesis:2013-4032
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 01 Mar 2013 10:59
• Last Modified: 01 Mar 2013 11:06
• URI: https://theses.gla.ac.uk/id/eprint/4032