Ceramide-1-phosphate and its transfer proteins in eukaryotes

Ceramide-1-phosphate (C1P) is a bioactive phosphorylated sphingolipid (SL), produced through the direct phosphorylation of ceramide by ceramide kinase. It plays important roles in regulating cell survival, migration, apoptosis and autophagy and is involved in inflammasome assembly/activation, which can stimulate group IVA cytosolic phospholipase A2α and subsequently increase the levels of arachidonic acid and pro-inflammatory cytokines. Human C1P transfer protein (CPTP) can selectively transport C1P from the Golgi apparatus to specific cellular sites through a non-vesicular mechanism. Human CPTP also affects specific SL levels, thus regulating cell SL homeostasis. In addition, human CPTP plays a crucial role in the regulation of autophagy, inflammation and cell death; thus, human CPTP is closely associated with autophagy and inflammation-related diseases such as cardiovascular and neurodegenerative diseases, and cancers. Therefore, illustrating the functions and mechanisms of human CPTP is important for providing the research foundations for targeted therapy. The key human CPTP residues for C1P recognition and binding are highly conserved in eukaryotic orthologs, while the human CPTP homolog in Arabidopsis (accelerated cell death 11) also exhibits selective inter-membrane transfer of phyto-C1P. These results demonstrate that C1P transporters play fundamental roles in SL metabolism in cells. The present review summarized novel findings of C1P and its TPs in eukaryotes.