The role of PIKfyve in toll-like receptor-mediated responses

Abstract

PIKfyve is the only kinase that phosphorylates the 5′-position of phosphatidylinositol (PtdIns) 3-phosphate to produce PtdIns (3,5)-bisphosphate, which is indispensable for intracellular traffi cking. Thus, this kinase is a potential regulator of various cellular events, such as autophagy, stress-mediated responses, and membrane and ion transport. However, little is known about the physiological function of PIKfyve in innate immune responses. A chemical that has been subjected to clinical tests for autoimmune diseases for the last decade was recently identified as a PIKfyve inhibitor. Additionally, in 2013, a few studies reported some roles of PIKfyve in Toll-like receptor-mediated responses. Although the reported findings are convincing and interesting, the interpretation of the function of PIKfyve based on these reports remains contradictory. In this review, we survey these reports together with data from the clinical tests of the PIKfyve inhibitor and present our perspective on the role of PIKfyve in innate immunity.