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Open AccessFeature PaperReview

The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors

1
Institute of Molecular and Cell Biology, Singapore 138673, Singapore
2
Centre for Mechanochemical Cell Biology, Warwick Medical School, Coventry CV4 7AL, UK
3
Department of Biochemistry, National University of Singapore, Singapore 119077, Singapore
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 915; https://doi.org/10.3390/cells8080915
Received: 2 July 2019 / Revised: 13 August 2019 / Accepted: 13 August 2019 / Published: 16 August 2019
(This article belongs to the Special Issue Membrane Traffic in Health and Disease)
Various growth factors and full-length cell surface receptors such as EGFR are translocated from the cell surface to the nucleoplasm, baffling cell biologists to the mechanisms and functions of this process. Elevated levels of nuclear EGFR correlate with poor prognosis in various cancers. In recent years, nuclear EGFR has been implicated in regulating gene transcription, cell proliferation and DNA damage repair. Different models have been proposed to explain how the receptors are transported into the nucleus. However, a clear consensus has yet to be reached. Recently, we described the nuclear envelope associated endosomes (NAE) pathway, which delivers EGFR from the cell surface to the nucleus. This pathway involves transport, docking and fusion of NAEs with the outer membrane of the nuclear envelope. EGFR is then presumed to be transported through the nuclear pore complex, extracted from membranes and solubilised. The SUN1/2 nuclear envelope proteins, Importin-beta, nuclear pore complex proteins and the Sec61 translocon have been implicated in the process. While this framework can explain the cell surface to nucleus traffic of EGFR and other cell surface receptors, it raises several questions that we consider in this review, together with implications for health and disease. View Full-Text
Keywords: EGFR; nuclear associated endosomes (NAE); insulin receptor; nuclear envelope; SUN; translocon EGFR; nuclear associated endosomes (NAE); insulin receptor; nuclear envelope; SUN; translocon
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Shah, P.; Chaumet, A.; Royle, S.J.; Bard, F.A. The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors. Cells 2019, 8, 915.

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