RME-8 regulates trafficking of the epidermal growth factor receptor.
We recently identified receptor-mediated endocytosis 8 (RME-8), a DnaJ domain protein localized to endosomes. We now demonstrate that RME-8 depletion leads to decreased levels of epidermal growth factor receptor (EGFR) without influencing receptors that primarily recycle to the plasma membrane. Decreases in EGFR are detected at both surface and intracellular pools and result from increased rates of EGFR degradation. Interestingly, RME-8 depletion also decreases EGFR levels in breast cancer cell lines in which overexpression of the EGFR family member ErbB2 has been shown to protect EGFR from degradation. These data implicate RME-8 in sorting decisions influencing EGFR at the level of endosomes and point to RME-8 as a potential regulatory target in ErbB2-positive breast cancers.
Girard
Martine
M
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.
McPherson
Peter S
PS
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology; D019556:COS Cells; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000201:enzymology*; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
D066246:ErbB Receptors; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C507525:DNAJC13 protein, human