A novel role for jun N-terminal kinase signaling in olfactory sensory neuronal death.
Olfactory sensory neurons (OSNs) represent a unique population of neurons in which death and regeneration are ongoing throughout adulthood, a feature that makes them an attractive model cell type for the investigation of neuronal death. However, the mechanism by which OSNs die remains elusive. Therefore, we developed a culture system for studying pathways involved in OSN death. Here, we show that inhibition of transcription or translation, by actinomycin D or cycloheximide, respectively, suppresses pathways leading to death, prolonging the survival of OSNs in culture. We discovered that caspase activity and jun N-terminal kinase (JNK) signaling both play a role in OSN death, and inhibition of JNK activity suppresses effector caspase (caspase-3) activation. Results from studies in culture were confirmed in vivo, in a mouse bulbectomy-induced OSN death model. These findings provide new insights into the nature of OSN death and a means of studying OSNs in vitro.
Department of Biological Sciences, Columbia University, NY, NY, USA.
Nidhi M
NM
Gangadhar
Stuart J
SJ
Firestein
Brent R
BR
Stockwell
D000818:Animals; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000201:enzymology*; D009830:Olfactory Bulb / Q000201:enzymology; D018034:Olfactory Receptor Neurons / Q000201:enzymology*
D048031:JNK Mitogen-Activated Protein Kinases