Lipid signaling

Lipids transduce signals from membranes

Although widely regarded as inert, lipids are in fact potent mediators of signal transduction. A striking example is the lipid A domain of bacterial lipopolysaccharide (LPS; also known as endotoxin) – a modified membrane phospholipid in Gram-negative organisms that contributes to septic shock (p. 299). A serum LPS-binding protein presents the endotoxin molecule to CD14-expressing monocyte-macrophages and neutrophils, leading to nonspecific immune recognition followed by activation of blood clotting and host defenses. Non-LPS immunogenic microbial lipids include lipoteichoic acid and lipoarabinomannan.

Lipid signaling molecules often have composite structures that include sugar and/or protein regions. The latter may include SH2 domains, which provide a mechanism for integrating lipid signaling with other biochemical response pathways. Signaling molecules may thus be formed from a variety of membrane-associated lipids including phosphatidylinositol, PIP2, phosphatidylcholine (lecithin), and phosphatidic and lysophosphatidic acid. The most abundant of these lipid phosphates is the monophosphorylated phosphatidylinositol-3-phosphate (PIP), which recruits endosomal and signaling proteins to the membrane via its interaction with a specific PIP-docking motif termed a FYVE domain.