Cloning, purification and characterisation of the extracellular domains of BAI1 protein (#307)
The clearance of apoptotic cells is essential for the maintenance of tissue homeostasis and development of the body (Nagata et al, 2010). This disposal is usually fast and well-organized. However, studies have shown that under failed or defective clearance, uncleared apoptotic cells contribute to a range of disease processes linked with diverse inflammatory diseases, autoimmunity and cancer (Ravichandran, 2011).
Uncleared apoptotic cells can undergo secondary necrosis and play a role in pathogenesis, respiratory diseases, neurological diseases, and tumorigenesis (Hochreiter-Hufford et al, 2013)
In the last decade, studies have provided more knowledge regarding the fundaments of apoptotic cell clearance. These studies have highlighted the importance of a prompt and efficient disposal, promoting anti-inflammatory responses and immunological tolerance (Henson & Bratton, 2013).
According to the World Health Organisation (2003), global cancer rates could increase by 50% in 2015 which makes urgent the necessity for new and alternative treatments. Therefore, the study of mechanisms that regulate apoptotic cell clearance in a range of species, from model organisms to humans is so important.
Brain-specific angiogenesis inhibitor 1 (BAI1) protein has been proposed to play an important role in the clearance of apoptotic cells by the binding of phosphatidylserine through the thrombospondin type 1 repeats (TSR) domains in its extracellular region. Also BAI1 protein has been suggested to promote the activation of the actin cytoskeleton of the phagocytes inducing the engulfment of dying cells (Park et al, 2007).
BAI1 protein has been studied for its angiogenic properties as well as its pro-apoptotic features, which facilitate recognition and engulfment of apoptotic cells.
The TSRs within the extracellular region of BAI1 have been identified to mediate direct binding to PS, acting as cell receptor of this membrane lipid. Nevertheless, the crystal structures of BAI1’s TSRs have not been solved to date, which difficult the determination of how this binding occurs or where it takes place.