Odin (ANKS1A) Modulates EGF Receptor Recycling and Stability |
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| Authors: | Jiefei Tong Yaroslav Sydorskyy Jonathan R St-Germain Paul Taylor Ming S Tsao Michael F Moran |
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| Institution: | 1. Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Canada.; 2. Department of Molecular Genetics, University of Toronto, Toronto, Canada.; 3. Department of Medical Biophysics, University of Toronto, Toronto, Canada.; 4. Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.; 5. Ontario Cancer Institute, University Health Network, Toronto, Canada.; Hungarian Academy of Sciences, Hungary, |
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| Abstract: | The ANKS1A gene product, also known as Odin, was first identified as a tyrosine-phosphorylated component of the epidermal growth factor receptor network. Here we show that Odin functions as an effector of EGFR recycling. In EGF-stimulated HEK293 cells tyrosine phosphorylation of Odin was induced prior to EGFR internalization and independent of EGFR-to-ERK signaling. Over-expression of Odin increased EGF-induced EGFR trafficking to recycling endosomes and recycling back to the cell surface, and decreased trafficking to lysosomes and degradation. Conversely, Odin knockdown in both HEK293 and the non-small cell lung carcinoma line RVH6849, which expresses roughly 10-fold more EGF receptors than HEK293, caused decreased EGFR recycling and accelerated trafficking to the lysosome and degradation. By governing the endocytic fate of internalized receptors, Odin may provide a layer of regulation that enables cells to contend with receptor cell densities and ligand concentration gradients that are physiologically and pathologically highly variable. |
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