LICAMM The role of Rab46 in cardiovascular disease

Summary

Endothelial cells line the blood vessels and play a central role in vascular function. Weibel Palade bodies (WPBs) are specialized storage vesicles found specifically in endothelial cells (1). These vesicles contain a pool of readily made cargo that, upon release, control vascular events such as haemostasis, inflammation, angiogenesis and vascular tone. Inappropriate release of WPB cargo into the blood vessel lumen results in the pro-inflammatory and pro-thrombotic environment associated with cardiovascular disease. My research involves understanding the mechanisms underlying the release of WPB cargo and how these become perturbed in cardiovascular disease.

Recently, we described a novel Rab GTPase (Rab46) in endothelial cells that has GTPase and Ca2+ binding activities and is located on WPBs (2)(2). Thereby, this research project involves a range of techniques including;- cell culture, siRNA transfection, calcium imaging, biochemistry, MRI and confocal microscopy, to address the role of Rab46 in WPB trafficking and endothelial cell secretion. In addition, we will investigate how mutations in this protein may contribute to cardiovascular diseases and explore the association of Rab46 with other inflammatory diseases using data from the UK Biobank.

References:

Weibel, E. R. (2012) Fifty years of Weibel-Palade bodies: the discovery and early history of an enigmatic organelle of endothelial cells. Journal of thrombosis and haemostasis : JTH 10, 979-984

Wilson, L. A., McKeown, L., Tumova, S., Li, J., and Beech, D. J. (2015) Expression of a long variant of CRACR2A that belongs to the Rab GTPase protein family in endothelial cells. Biochemical and biophysical research communications 456, 398-402

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