Ceramide in Stem Cell Differentiation and Embryo Development: Novel Functions of a Topological Cell-Signaling Lipid and the Concept of Ceramide Compartments
Figure 3
A core complex associated with ceramide may regulate cell polarity. (a) Ceramide microdomains or rafts may be formed after local hydrolysis of sphingomyelin catalyzed by acid or neutral sphingomyelinase. PIP2 or 3 embedded in these ceramide microdomains may bind to Cdc42 (via PH domain), while ceramide-associated aPKC binds to Par6. The formation of a SphingoLipid (here ceramide)-Induced Protein Scaffold (SLIPS) then regulates the dynamics of the cytoskeleton via additional proteins such as GSK-3β. This may sustain ceramide-rich platforms (e.g., in the apical membrane of primitive ectoderm cells) or initiate processes (“sphingopodia”) in neural stem and progenitor cells. The image on the right panel shows staining of ceramide microdomains using a ceramide-specific antibody generated in our laboratory. Note that the plus end of microtubules appears to attach to the ceramide domains. (b) Likewise, we have found that a pericentriolar, apical ceramide-enriched compartment (ACEC) appears to be attached to the basal body of the primary cilium. The right panel shows the ring-shaped structure of this compartment that we have termed “sphingosome”. (c) We hypothesize that a ceramide-aPKC polarity complex (CAP-PC) consisting of ceramide, aPKC, Par6, Cdc42, and Par3 forms a functional key element of many cell polarity-related processes including cell adhesion, process formation (“sphingopodia”), cell migration, and ciliogenesis. The local assembly of distinct sphingolipid-induced protein scaffolds (SLIPs) determines the functional specificity of this polarity complex.
