Modulation of Ion Channels and Receptors by p11 (S100A10)

p11 (S100A10, annexin II light chain, calpactin I light chain) is a multifunctional protein that forms a heterotetrameric complex with Annexin A2, particularly at cell membranes. p11, alone or together with Annexin A2, interacts with several ion channels and receptors and regulates their cellular localization and function. Altered levels of p11 are implicated in the pathophysiology of several forms of cancer, psychiatric disorders, and neurodegeneration. Via interactions with ion channels and receptors, p11 modulates therapeutic actions of drugs targeting brain disorders. By serving as a plasminogen receptor, p11 plays an important role in plasmin generation, fibrinolysis, angiogenesis, tumor progression, and metastasis. Here, we review mechanisms whereby p11 regulates functions of ion channels and receptors in health and disease states. The level of p11 is altered in psychiatric and neurological disorders and in various forms of cancer.Via multiple interactions with annexin A2, ion channels, and receptors, p11 is implicated in the pathophysiology of several disease states, but also in mediating therapeutic drug responses.p11 stands out as a versatile modulator of ion channels and receptors as it interacts with several distinct ion channels and receptors via a range of different mechanisms.p11 is critical for the generation of plasmin from plasminogen, which regulates fibrinolysis, angiogenesis, and tumor progression.Identification of interfaces in interactions between p11, annexin A2, and ion channels or receptors that provide pharmacophores may offer novel therapeutic targets against neurological disorders and several forms of cancer.