Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells.
Execution of physiologic cell death known as apoptosis is tightly regulated and transfers immunologically relevant information. This ensures efficient clearance of dying cells and shapes the phenotype of their "captors" toward anti-inflammatory. Here, we identify a mechanism of sphingosine-1-phosphate production by apoptotic cells. During cell death, sphingosine kinase 2 (SphK2) is cleaved at its N-terminus in a caspase-1-dependent manner. Thereupon, a truncated but enzymatically active fragment of SphK2 is released from cells. This step is coupled to phosphatidylserine exposure, which is a hallmark of apoptosis and a crucial signal for phagocyte/apoptotic cell interaction. Our data link signaling events during apoptosis to the extracellular production of a lipid mediator that affects immune cell attraction and activation.
Weigert
Andreas
A
Institute of Biochemistry I/Zentrum für Arzneimittelforschung, -Entwicklung und -Sicherheit (ZAFES), Goethe-University Frankfurt, Frankfurt, Germany
Cremer
Sarah
S
Schmidt
Martina Victoria
MV
von Knethen
Andreas
A
Angioni
Carlo
C
Geisslinger
Gerd
G
Brüne
Bernhard
B
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D008246:Lysophospholipids / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000276:immunology* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D000099157:Sphingosine Kinase
D020170:Caspase 1; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate