The Annexin A2/S100A10 Complex: The Mutualistic Symbiosis of Two Distinct Proteins

Abstract

Mutualistic symbiosis refers to the symbiotic relationship between individuals of different species in which both individuals benefit from the association. S100A10, a member of the S100 family of Ca2+-binding proteins, exists as a tight dimer and binds two annexin A2 molecules. This association forms the annexin A2/S100A10 complex known as AIIt, and modifies the distinct functions of both proteins. Annexin A2 is a Ca2+-binding protein that binds F-actin, phospholipid, RNA, and specific polysaccharides such as heparin. S100A10 does not bind Ca2+, but binds tPA, plasminogen, certain plasma membrane ion channels, neurotransmitter receptors, and the structural scaffold protein, AHNAK. S100A10 relies on annexin A2 for its intracellular survival: in the absence of annexin A2, it is rapidly destroyed by ubiquitin-dependent and independent proteasomal degradation. Annexin A2 requires S100A10 to increase its affinity for Ca2+, facilitating its participation in Ca2+-dependent processes such as membrane binding. S100A10 binds tissue plasminogen activator and plasminogen, and promotes plasminogen activation to plasmin, which is a process stimulated by annexin A2. In contrast, annexin A2 acts as a plasmin reductase and facilitates the autoproteolytic destruction of plasmin. This review examines the relationship between annexin A2 and S100A10, and how their mutualistic symbiosis affects the function of both proteins.