Accumulated evidence indicates that PtdIns5P, one of the seven phosphoinositides, found now to be constitutively present in yeast, plants and metazoa, serves as a signaling molecule to modulate pleiotropic cellular functions in both the nucleus and the cytoplasm. The enzymatic routes in biogenesis of basal PtdIns5P have remained incompletely understood. The role for candidate kinase PIKfyve that is principally involved in PtdIns(3,5)P2 production, has been questioned. In this review article we scrutinize the past obstacles that prevented the definitive implication of PIKfyve in PtdIns5P biosynthesis from PtdIns and focus on the recent pharmacological and genetic advancements that now make this conclusion well supported. We further summarize our current knowledge of the diverse stimuli modulating PtdIns5P levels, binding partners and regulated cellular process, with particular reference to the available mechanistic insights for the relevant signaling pathways.
Keywords: Actin cytoskeleton remodeling; Akt; Insulin-regulated glucose transport; MTM/MTMRs; Membrane trafficking; PI4-phosphatases; PIKfyve; PIP4-kinases; PtdIns5P; Stress responses.
Copyright © 2013. Published by Elsevier Inc.