Odin (ANKS1A) modulates EGF receptor recycling and stability

PLoS One. 2013 Jun 25;8(6):e64817. doi: 10.1371/journal.pone.0064817. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Endosomes / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Flow Cytometry
  • Humans
  • Immunoprecipitation
  • Mass Spectrometry
  • Phosphorylation
  • Protein Transport / genetics
  • Protein Transport / physiology

Substances

  • ANKS1A protein, human
  • Adaptor Proteins, Signal Transducing
  • EGFR protein, human
  • ErbB Receptors