The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/8/915 |
| _version_ | 1827887312866902016 |
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| author | Poonam Shah Alexandre Chaumet Stephen J. Royle Frederic A. Bard |
| author_facet | Poonam Shah Alexandre Chaumet Stephen J. Royle Frederic A. Bard |
| author_sort | Poonam Shah |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T20:16:26Z |
| format | Article |
| id | doaj.art-4eacf8bd83494c77887ada1bcc064062 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T20:16:26Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4eacf8bd83494c77887ada1bcc0640622023-08-02T01:17:11ZengMDPI AGCells2073-44092019-08-018891510.3390/cells8080915cells8080915The NAE Pathway: Autobahn to the Nucleus for Cell Surface ReceptorsPoonam Shah0Alexandre Chaumet1Stephen J. Royle2Frederic A. Bard3Institute of Molecular and Cell Biology, Singapore 138673, SingaporeInstitute of Molecular and Cell Biology, Singapore 138673, SingaporeCentre for Mechanochemical Cell Biology, Warwick Medical School, Coventry CV4 7AL, UKInstitute of Molecular and Cell Biology, Singapore 138673, SingaporeVarious 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.https://www.mdpi.com/2073-4409/8/8/915EGFRnuclear associated endosomes (NAE)insulin receptornuclear envelopeSUNtranslocon |
| spellingShingle | Poonam Shah Alexandre Chaumet Stephen J. Royle Frederic A. Bard The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors Cells EGFR nuclear associated endosomes (NAE) insulin receptor nuclear envelope SUN translocon |
| title | The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors |
| title_full | The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors |
| title_fullStr | The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors |
| title_full_unstemmed | The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors |
| title_short | The NAE Pathway: Autobahn to the Nucleus for Cell Surface Receptors |
| title_sort | nae pathway autobahn to the nucleus for cell surface receptors |
| topic | EGFR nuclear associated endosomes (NAE) insulin receptor nuclear envelope SUN translocon |
| url | https://www.mdpi.com/2073-4409/8/8/915 |
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