Ceramide 1-phosphate phosphatase activity in brain.
Recent studies have implicated sphingolipids in a variety of intracellular signaling systems. The finding that a calcium-stimulated ceramide kinase copurifies with neurotransmitter-containing vesicles suggests that ceramide, or one of its metabolites, has a role in neurotransmitter release. As a step toward understanding the role of ceramide kinase in vesicle functioning, this study sought to determine the metabolic fate of the product, ceramide 1-phosphate. We report that ceramide 1-phosphate is not deacylated by brain ceramidases to produce sphingosine 1-phosphate. It is, however, the substrate for a phosphatase activity that we name ceramide 1-phosphate phosphatase (CPPase). Subcellular fractionation studies suggest that CPPase is found in the synaptic terminal and is associated with both synaptic vesicle and plasma membranes. Divalent cations, most notably calcium, inhibit CPPase activity although not at concentrations that activate ceramide kinase. The existence of both ceramide kinase and CPPase activities at the synapse suggests that ceramide 1-phosphate production regulates some aspect of synaptic vesicle functioning.
Shinghal
R
R
Department of Molecular and Cellular Physiology, Stanford University, California 94305-5428.
Scheller
R H
RH
Bajjalieh
S M
SM
D000581:Amidohydrolases / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D002458:Cell Fractionation; D055572:Ceramidases; D002518:Ceramides / Q000138:chemical synthesis / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D010744:Phosphoric Monoester Hydrolases / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D013107:Sphingolipids / Q000378:metabolism; D013379:Substrate Specificity; D013574:Synaptosomes / Q000201:enzymology*
D002518:Ceramides; D013107:Sphingolipids; C065576:ceramide 1-phosphate; C083741:ceramide-1-phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D000581:Amidohydrolases; D055572:Ceramidases; D002118:Calcium