The translocon Sec61β localized in the inner nuclear membrane transports membrane-embedded EGF receptor to the nucleus

Ying Nai Wang, Hirohito Yamaguchi, Longfei Huo, Yi Du, Hong Jen Lee, Heng Huan Lee, Hongmei Wang, Jung Mao Hsu, Mien Chie Hung

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Accumulating evidence indicates that endocytosis plays an essential role in the nuclear transport of the ErbB family members, such as epidermal growth factor receptor (EGFR) and ErbB-2. Nevertheless, how full-length receptors embedded in the endosomal membrane pass through the nuclear pore complexes and function as non-membrane-bound receptors in the nucleus remains unclear. Here we show that upon EGF treatment, the biotinylated cell surface EGFR is trafficked to the inner nuclear membrane (INM) through the nuclear pore complexes, remaining in a membrane-bound environment. We further find that importin β regulates EGFR nuclear transport to the INM in addition to the nucleus/nucleoplasm. Unexpectedly, the well known endoplasmic reticulum associated translocon Sec61β is found to reside in the INM and associate with EGFR. Knocking down Sec61β expression reduces EGFR level in the nucleoplasm portion and accumulates it in the INM portion. Thus, the Sec61β translocon plays an unrecognized role in the release of the membrane-anchored EGFR from the lipid bilayer of the INM to the nucleus. The newly identified Sec61β function provides an alternative pathway for nuclear transport that can be utilized by membrane-embedded proteins such as full-length EGFR.

Original languageEnglish (US)
Pages (from-to)38720-38729
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number49
DOIs
StatePublished - Dec 3 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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