Ceramide-rich platforms in transmembrane signaling

Abstract

Recent evidence suggests that ceramide regulates stress signaling via reorganization of the plasma membrane. The focus of this review will be to discuss the mechanism by which acid sphingomyelinase (ASMase)-generated ceramide initiates transmembrane signaling in the plasma membrane exoplasmic leaflet. In particular, we review the unique biophysical properties of ceramide that render it proficient in formation of signaling domains termed ceramide-rich platforms (CRPs), and the role of CRPs in the pathophysiology of various diseases. The biomedical significance of CRPs makes these structures an attractive therapeutic target.

Figure 1. Ceramide-rich platform formation in a model membrane

Still fluorescent microscopy images depicting membrane reorganization of SOPC:C16-0 SM:Bdp-SM (0:75:0.2:0.05) GUV (A) following ceramide formation by SMase coupled onto amino-derivatized acrylate (B-F). Contacting membrane surface with immobilized SMase (B) resulted in generation of ceramide patches in one pole of the GUV depicted at 45 min (C), 50 min (D), 55 min (E) and 90 min (F). Adapted from Nurminen et al. JACS, 2002 [39]

Figure 2. Ceramide-rich platforms in murine tracheal epithelial cells following in vivo infection with Pseudomonas aeruginosa

Fluorescence microscopy images demonstrate colocalization of surface ceramide with Pseudomonas aeruginosa and ASMase on the cilia of in vivo-infected murine tracheal epithelial cells at 20 minutes post infection. Adapted from Grassme et al. Nature Medicine, 2003 [94]