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. [BMB Reports 2014; 47(7): 361-368]

Shotgun Lipidomics Revealed Altered Profiles of Serum Lipids in Systemic Lupus Erythematosus Closely Associated with Disease Activity

“…PI and its derivatives regulate many vital cell processes, such as membrane dynamics, fusion, and trafficking, as well as serving as precursors of second messengers in signal transduction [30]. Recent evidence indicates that PI involves Toll-like receptor signaling, which is very important for the innate immune response and is implicated in diverse pathophysiological disorders [31]. Therefore, the metabolism of PI species in serum of SLE patients could be characteristic and representative since SLE pathogenesis is largely due to dysfunction of immunocytes.…”

Emerging Risk Biomarkers in Cardiovascular Diseases and Disorders

“…More importantly, coadministration of probucol with atorvastatin did not affect the antioxidative effects of probucol. Probucol has significant add-on antiatherosclerotic effects when combined with atorvastatin treatment [ 340 ].…”

An inhibitory alternative splice isoform of Toll-like receptor 3 is induced by type I interferons in human astrocyte cell lines

“…Astrocytes perform a variety of physiological functions such as forming the blood-brain barrier, transporting nutrients, and maintaining ion balances for the normal physiology of the brain. In addition, astrocytes play an important role in diseases related to neuro-inflammation (14 , 15) . Astrocytes express numerous PRRs to allow for the recognition of diverse pathogen-associated molecular patterns (PAMPs) (16 - 18) .…”