Biological functions of sphingomyelins

Abstract

Sphingomyelin (SM) is a dominant sphingolipid in membranes of mammalian cells and this lipid class is specifically enriched in the plasma membrane, the endocytic recycling compartment, and the trans Golgi network. The distribution of SM and cholesterol among cellular compartments correlate. Sphingolipids have extensive hydrogen-bonding capabilities which together with their saturated nature facilitate the formation of sphingolipid and SM-enriched lateral domains in membranes. Cholesterol prefers to interact with SMs and this interaction has many important functional consequences. In this review, the synthesis, regulation, and intracellular distribution of SMs are discussed. The many direct roles played by membrane SM in various cellular functions and processes will also be discussed. These include involvement in the regulation of endocytosis and receptor-mediated ligand uptake, in ion channel and G-protein coupled receptor function, in protein sorting, and functioning as receptor molecules for various bacterial toxins, and for non-bacterial pore-forming toxins. SM is also an important constituent of the eye lens membrane, and is believed to participate in the regulation of various nuclear functions. SM is an independent risk factor in the development of cardiovascular disease, and new studies have shed light on possible mechanism behind its role in atherogenesis.

Keywords: Atherogenesis; CERT; CPE; ER; HDL; LCAT; LDL; Microdomains; Molecular species; OSBP; PC; PIP(2); SAC; SM; SMS; SMS knockout; SMSr; SMase; SPT; Sphingolipid biosynthesis; StnII; TMD; Tf; Toxin binding; ceramide phosphoethanolamine; ceramide transport protein; endoplasmic reticulum; high density lipoprotein; lecithin:cholesterol acyltransferase; low density lipoprotein; oxysterol binding protein; phosphatidylcholine; phosphatidylinositol-4,5-bisphosphate; serine palmitoyl transferase; sphingomyelin; sphingomyelin synthase; sphingomyelin synthase related protein; sphingomyelinase; sticholysine II; subapical compartment; transferrin; transmembrane domain.