Platelet adhesion and secretion
Although primarily recognized for their role in hemostasis and thrombosis, platelets are increasingly recognized as important players in inflammation and cancer progression. The mixed protein content in platelet secretory granules with both adhesive and inflammatory functions, as well as proteins that regulate new blood vessel formation makes it necessary that cargo secretion is precisely regulated. The molecular mechanism underlying the release of granule contents is incompletely understood. In the recent years we have combined cryo-immobilization techniques (High-Pressure Freezing, vitrification), and dual axis Electron Tomography to visualize cellular dynamics in a close to native environment. Using real-time imaging and 3D cryo-EM techniques we aim characterizing the timed release kinetics of secretory alpha granules.
We are currently developing new imaging methods to visualize the dynamics of platelet adhesion and secretion at the single cell level. These include live video microscopy, confocal microscopy, and correlative electron microscopy methods. The platelet secretory response is used as a model system for the further development of cellular cryo-EM. Within this field a 9 month master rotation project is available for students life sciences with a high interest in live cell imaging and 3D (cryo)-EM techniques.
Info: Dr. Harry F.G. Heijnen.
Key publications of our group ( Full list here)
Platelet secretory behaviour: As diverse as the granules ... or not?
Heijnen, H. & van der Sluijs, J. Thromb. Haem. 2015.
Biogenesis of the demarcation membrane system (DMS) in megakaryocytes.
Eckly et al., Blood. 2014
Lysosome-related organelles: unusual compartments become mainstream.
Marks, M., Heijnen, H. & Raposo, G. Current Opinion in Cell Biology. 2013.
Endosome-mediated autophagy: An unconventional MIIC-driven autophagic pathway operational in dendritic cells.
Kondylis et al., Autophagy.2013.
The platelet interior revisited: electron tomography reveals tubular alpha-granule subtypes.
van Nispen tot Pannerden et al., Blood. 2010.