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KMID : 0578320130350050450
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Molecules and Cells
2013 Volume.35 No. 5 p.450 ~ p.455
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EphrinA5-EphA7 Complex Induces Apoptotic Cell Death Via TNFR1
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Lee Hae-Ryung
Park Eun-Jeong
Kim Yu-Jin
Park Soo-Chul
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Abstract
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A previous study showed that the EphA7 receptor regu-lates apoptotic cell death during early brain development. In this study, we provide evidence that the EphA7 receptor interacts with death receptors such as tumor necrosis factor receptor 1 (TNFR1) to decrease cell viability. We showed that ephrinA5 stimulates EphA7 to activate the TNFR1-mediated apoptotic signaling pathway. In addition, a pull-down assay using biotinylated ephrinA5-Fc revealed that ephrinA5-EphA7 complexes recruit TNFR1 to form a multi-protein complex. Immunocytochemical staining ana-lysis showed that EphA7 was co-localized with TNFR1 on the cell surface when cells were incubated with ephrinA5 at low temperatures. Finally, both the internalization motif and death domain of TNFR1 was important for inter-acting with an intracytoplasmic region of EphA7; this interaction was essential for inducing the apoptotic signaling cascade. This result suggests that a distinct multi-protein complex comprising ephrinA5, EphA7, and TNFR1 may constitute a platform for inducing caspase-dependent apoptotic cell death.
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KEYWORD
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apoptosis, ephrinA5, EphA7, TNFR1
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