The action and regulation of Sphingomyelinase in lipid membranes

MARIA L. FANANI; BRUNO MAGGIO

Tucuman

Simposio; XLI Reunion Annual Sociedad Argentina de Biofísica, Simposio Red CYTED-Biotox; 2012

Sociedad Argentina de Biofísica, Red CITED BIOTOX

Sphingomyelinase (SMase) is a phospholipase that hydrolyzes sphingomyelin producing ceramide, which remains in the membrane, and the water-soluble phosphocholine. It is present in bacterial hemolytic cocktails, spider venoms and has an important role in mammalian cell signal transduction. The production of ceramide induces important changes in the physical organization of the membrane, which is proposed as its main biological function. In cholesterol-poor membranes the enzymatically produced ceramide laterally segregates forming condensed ceramide-enriched domains (1) whose composition and morphology depends on the kinetics of ceramida production (2). On the other hand, in cholesterol-rich membranes the produced ceramide partitions preferentially in cholesterol-rich liquid-ordered domains, freeing the more expanded (SMase-rich) active phase from product and allowing the liquid-ordered domains to act as substrate reservoir. As a consequence SMase shows an enhanced activity when acting in a membrane that exhibit the coexistence of liquid-expanded/ liquid-ordered phases (3) compared to fully liquid-expanded or fully liquid-ordered phases. Therefore, lipid diffusion and preferential partitioning in the different phases determine the membrane reactivity, dynamics and bi-dimensional structure that are relevant for the enzymatic function.