Close interrelationship of sphingomyelinase and caveolin in triton x-100-lnsoluble membrane microdomains

Abstract

Much attention has been paid to the roles of sphingomyelin (SM) metabolism in the regulation of various cell functions such as cell growth, differentiation and apoptosis. Sphingomyelinase (SMase) catalyzes the first step of SM-metabolizing pathways that generate the bioactive metabolite, ceramide. SMase present in membrane microdomains, raft and caveolae may be involved in the agonist-mediated events. However, it is still unclear which molecular species of SMase is stimulated by an agonist to produce ceramide in membrane microdomains, and how agonist-sensitive SMase and SM are topologically localized within the micro-domains. Here, we first show the close interaction between neutral SMase and caveolin 1 in 1% Triton X-100-insoluble fractions of plasma membranes isolated from adult rat resting liver and rapidly growing rat ascites hepatoma, AH 7974 cells. Then, we describe the connection between acid SMase and caveolin 2 in cell differentiation or apoptosis induced by all-trans retinoic acid. Finally, we discuss the possible roles for caveolins with respect to the topological distribution of SMase and SM in caveolae. © Springer-Verlag Tokyo 2006. All rights reserved.