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Global riactice Leader's in Brain Science

7/17 (Tue) 16:00 Special Seminar
Name : 관리자 | Date : 2018.07.16 09:18 | Views : 8859

Title: The p38 MAPK Pathway Modulates The Hypoxia Response and Glutamate Receptor Trafficking


Speaker: Eunchan Park, Ph.D., Waksman Institute, Rutgers University (Host : Kyuhyung Kim)


Time: 16:00, July 17 (Tue), 2018
        

Venue: Room 114, Building E4, DGIST


Abstract : Hypoxia (low O2) plays a central role in a diverse array of human diseases. O2 is sensed by the hypoxia response pathway comprising a prolyl hydroxylase (PHD) enzyme, which uses O2 to hydroxylate specific prolines on the Hypoxia Inducible Factorα(HIFα). Once hydroxylated, HIFα is ubiquitinated by the Von Hippel-Lindau (VHL) ubiquitin ligase, resulting in its proteolysis. When hypoxia ensues, PHD enzymes lack the O2 to hydroxylate HIFα, resulting in HIFα stabilization, entry into the nucleus, and the transcriptional regulation of multiple target genes. Because of the essential requirement of pathway components in early development and viability in mammals, we know little about how the pathway works in vivo in an intact animal.
C. elegans is broadly tolerant to oxygen levels; therefore, it is an excellent system to study the hypoxia response pathway.
Here, we show that p38 MAP Kinase (MAPK) modulates this hypoxia response pathway in C. elegans. Mutants lacking p38 MAPK components pmk-1 or sek-1 resemble mutants lacking the hypoxia response component and prolyl hydroxylase egl-9, with impaired subcellular localization of Mint orthologue LIN-10, internalization of glutamate receptor GLR-1, and depression of GLR-1-mediated behaviors. Loss of p38 MAPK impairs EGL-9 protein localization in neurons and activates the hypoxia-inducible transcription factor HIF-1/ HIFα, suggesting that p38 MAPK inhibits the hypoxia response pathway through EGL-9. As animals age, p38 MAPK levels decrease, resulting in GLR-1 internalization; this age-dependent downregulation can be prevented through either p38 MAPK overexpression or removal of CDK-5, an antagonizing kinase. Our findings demonstrate that p38 MAPK inhibits the hypoxia response pathway and determines how aging neurons respond to hypoxia through a novel mechanism.

 


Person in charge : Sora Lee


Contact: srlee@dgist.ac.kr, 053)785-6102

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