The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR

J Cell Biol. 2016 Nov 21;215(4):543-558. doi: 10.1083/jcb.201601090. Epub 2016 Nov 8.

Abstract

Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown. In this study, we find that EGF stimulation specifically increases the transport efficiency of newly synthesized EGFRs from the endoplasmic reticulum to the plasma membrane. This coincides with an up-regulation of the inner coat protein complex II (COPII) components SEC23B, SEC24B, and SEC24D, which we show to be specifically required for EGFR transport. Up-regulation of these COPII components requires the transcriptional regulator RNF11, which localizes to early endosomes and appears additionally in the cell nucleus upon continuous EGF stimulation. Collectively, our work identifies a new regulatory mechanism that integrates the degradation and transport of EGFR in order to maintain its physiological levels at the plasma membrane.

MeSH terms

  • COP-Coated Vesicles / drug effects
  • COP-Coated Vesicles / metabolism
  • Carrier Proteins / metabolism*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Endosomes / drug effects
  • Endosomes / metabolism*
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / metabolism*
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / metabolism
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Transport / drug effects
  • Proteolysis* / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Transcription, Genetic* / drug effects
  • Up-Regulation / drug effects

Substances

  • Carrier Proteins
  • RNF11 protein, human
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Epidermal Growth Factor
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt