The cell biology of the SARS coronavirus receptor, angiotensin-converting enzyme 2

Abstract

The identification of angiotensin-converting enzyme 2 (ACE2) as a cellular receptor for the SARS coronavirus (SARS-CoV) rejuvenated research into what was regarded by some as a minor player in the renin-angiotensin system. The discovery of its double life led to breathtaking advances in the understanding of virtually all aspects of its biology, including its structure, physiological and pathophysiological roles and cell biology. ACE2, like its well-known homologue, ACE, is a metallopeptidase which resides on the cell surface of the epithelial, and sometimes endothelial, cells of the heart, kidney, testes, lung and gastrointestinal tract. It is a type I transmembrane protein with a large catalytic extracellular domain which acts as both a peptidase and a viral receptor. This extracellular domain can be cleaved from the cell surface by other peptidases, modulating its activity. The levels of the enzyme on the cell surface are also thought to be regulated by internalisation on S-protein binding and by clustering in membrane microdomains known as lipid rafts. This chapter summarises the current understanding of how the cell biology of ACE2 is regulated and may influence and determine its function, and concludes by discussing the future challenges and opportunities for studies of this increasingly important enzyme. © 2010 Springer-Verlag Berlin Heidelberg.