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KMID : 0578320100290060603
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Molecules and Cells
2010 Volume.29 No. 6 p.603 ~ p.609
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EphA8-ephrinA5 Signaling and Clathrin-Mediated Endocytosis Is Regulated by Tiam-1, a Rac-Specific Guanine Nucleotide Exchange Factor
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Yoo Soo-Yeon
Shin Jong-Dae
Park Soo-Chul
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Abstract
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Recent studies indicate that endocytosis of Eph-ephrin complexes may be one of the mechanisms by which a high affinity cell-cell adhesion is converted to a repulsive interaction. In this study, we show that EphA8 undergoes clathrin-mediated endocytosis upon treatment with eph-rin- A5, and that EphA8 is associated tightly with Tiam-1, a Rac-specific guanine nucleotide exchange factor. Analysis of EphA8 deletion mutants revealed that a juxtamembrane region in EphA8 is critically involved in endocytosis of EphA8-ephrinA5 complexes. An EphA8 mutant lacking this juxtamembrane portion was defective for endocytosis with ephrinA5, and also displayed a weak association with Tiam-1. Expression of an endocytosis-defective version of EphA8 resulted in a low level of Rac activity in response to ephrin-A5 stimulation. More importantly, down-regulation of Tiam-1 resulted in inefficient endocytosis of EphA8-ephrinA5 complexes. These results suggest that Tiam-1 plays a role in clathrin-dependent endocytosis of EphA8-ephrinA5 complexes.
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KEYWORD
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endocytosis, EphA8, ephrin-A5
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