Involvement of CD137 ligand signaling in neural stem cell death.
CD137 is a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Interaction of CD137 with its ligand (CD137L) affects the apoptosis, proliferation and differentiation of immune cells. Interestingly, the CD137 receptor/ligand system involves the bi-directional transduction of signals. The expression of CD137 and its ligand is not restricted to immune organs, but can also be detected in a wide variety of tissues such as the brain, kidney, lung and heart. However, its role in brain is largely unknown. This study was performed to determine the role of CD137L reverse signaling in the apoptosis of neural stem cells. We identified the expression of CD137 and its ligand in C17.2 neural stem cells derived from mouse embryonic cerebellum. We found that the activation of CD137L reverse signaling by CD137 resulted in a decrease in cell adhesion to the fibronectin-coated culture basement, thus causing detachment-induced cell death. Furthermore, we showed that the cell death induced by CD137 was completely ameliorated by integrin activators and caspase inhibitors. Therefore we suggest that CD137L reverse signaling exerts a pro-apoptotic effect by suppressing integrin-mediated survival signals in neural stem cells.
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, 680-749, Korea.
Chang Ho
CH
Yun
Hye Myeong
HM
Lee
Sang Chul
SC
Lee
Byung Sam
BS
Kim
Jeong Woo
JW
Park
Byung Ju
BJ
Lee
D053330:4-1BB Ligand / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors / Q000494:pharmacology; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D002531:Cerebellum / Q000166:cytology* / Q000196:embryology; D005353:Fibronectins / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors; D051379:Mice; D058953:Neural Stem Cells / Q000502:physiology*; D015398:Signal Transduction; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology / Q000378:metabolism*
D053330:4-1BB Ligand; D061945:Caspase Inhibitors; D005353:Fibronectins; D016023:Integrins; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9