title: Phosphoinositide turnover in Toll-like receptor signaling and trafficking.
abstract: Lipid components in biological membranes are essential for maintaining cellular function. Phosphoinositides, the phosphorylated derivatives of phosphatidylinositol (PI), regulate many critical cell processes involving membrane signaling, trafficking, and reorganization. Multiple metabolic pathways including phosphoinositide kinases and phosphatases and phospholipases tightly control spatio-temporal concentration of membrane phosphoinositides. Metabolizing enzymes responsible for PI 4,5-bisphosphate (PI(4,5)P2) production or degradation play a regulatory role in Toll-like receptor (TLR) signaling and trafficking. These enzymes include PI 4-phosphate 5-kinase, phosphatase and tensin homolog, PI 3-kinase, and phospholipase C. PI(4,5)P2 mediates the interaction with target cytosolic proteins to induce their membrane translocation, regulate vesicular trafficking, and serve as a precursor for other signaling lipids. TLR activation is important for the innate immune response and is implicated in diverse pathophysiological disorders. TLR signaling is controlled by specific interactions with distinct signaling and sorting adaptors. Importantly, TLR signaling machinery is differentially formed depending on a specific membrane compartment during signaling cascades. Although detailed mechanisms remain to be fully clarified, phosphoinositide metabolism is promising for a better understanding of such spatio-temporal regulation of TLR signaling and trafficking.
authors.affiliation: Neuroscience Graduate Program, Department of Biomedical Sciences, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Gyeonggi 443-721, Korea.
authors.forename: Oanh Thi Tu
authors.initials: OT
authors.lastname: Le
authors.affiliation: Neuroscience Graduate Program, Department of Biomedical Sciences, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Gyeonggi 443-721, Korea.
authors.forename: Tu Thi Ngoc
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Neuroscience Graduate Program, Department of Biomedical Sciences, and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Gyeonggi 443-721, Korea.
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Lee
mesh_terms: D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; D051193:Toll-Like Receptors; D019869:Phosphatidylinositol 3-Kinases; D010740:Phospholipases