Molecular mechanism of the nuclear protein import cycle
Abstract
The nuclear import of proteins through nuclear pore complexes (NPCs) illustrates how a complex biological function can be generated by a spatially and temporally organized cycle of interactions between cargoes, carriers and the Ran GTPase. Recent work has given considerable insight into this process, especially about how interactions are coordinated and the basis for the molecular recognition that underlies the process. Although considerable progress has been made in identifying and characterizing the molecular interactions in the soluble phase that drive the nuclear protein import cycle, understanding the precise mechanism of translocation through NPCs remains a major challenge.
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In the absence of sumoylation, RanGAP1 is unable to bind RanBP2 or localize to the nuclear envelope.
“In the absence of sumoylation, RanGAP1 is unable to bind RanBP2 or localize to the nuclear envelope (Figure 4C, (31–33).”
From Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS (2025) · cites this paper as [33]
Importin-α acts as an adaptor protein that recognizes the NLS of cargo proteins and is transported as a ternary complex with importin-β into the nucleus.
“Importin-α is a constituent of the classical nuclear import pathway. It acts as an adaptor protein that recognizes the NLS of cargo proteins and is transported as a ternary complex with importin-β into the nucleus [39], [40]”
From UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner (2013) · cites this paper as [40]
Cargo protein with a classic NLS requires a direct interaction with importin-α to be transported through the nuclear pore complex.
“Cargo protein with a classic NLS requires a direct interaction with importin-α to be transported through the nuclear pore complex [31], [40], [45], [46], [47]”
From UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner (2013) · cites this paper as [40]
Transportation of cargo protein in importin-α/−β protein complexes through the NPC requires energy derived from the activities of GTPases.
“Transportation of cargo protein in importin-α/−β protein complexes through the NPC requires energy derived from the activities of GTPases [40], [45] (Figure 2A).”
From UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner (2013) · cites this paper as [40]
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UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner
Li, Z., Musich, P. R., Cartwright, B. M., Wang, H., & Zou, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068297 · Cited by 26 · see citing works
“transported as a ternary complex with importin-b into the nucleus [39,40] (Figure 2A).”
BackgroundMusich, P. R., Li, Z., & Zou, Y. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-56017-5_4 · Cited by 23 · see citing works
Nap1 and Chz1 have Separate Htz1 Nuclear Import and Assembly Functions
Straube, K., Blackwell, J. S., & Pemberton, L. F. (2010) · Traffic · doi:10.1111/j.1600-0854.2009.01010.x · Cited by 53 · see citing works
Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS
Bekier, M. E., Pinarbasi, E., Krishnan, G., Mesojedec, J. J., Hurley, M., Harikumar Sheela, H., Collins, C. A., Ghaffari, L., de Majo, M., Ullian, E. M., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci188138 · Cited by 2 · see citing works
“Nuclear localization of receptor-bound cargo is mediated by RanGAP1 and RanBP2, nuclear pore–associated factors that regulate the Ran gradient (33).”
- Authors
- Stewart, M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Stewart, Murray
- ORCID
- Stewart, Murray
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2007-02-07
- Volume
- 8
- Issue
- 3
- Pages
- 195-208
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2048492672
- Cited by
- 919
- References
- 101
- Citations by year
- 2026: 28 · 2025: 38 · 2024: 33 · 2023: 50 · 2022: 43 · 2021: 37 · 2020: 51 · 2019: 50 · 2018: 37 · 2017: 42 · 2016: 53 · 2015: 51 · 2014: 54 · 2013: 42 · 2012: 36
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- nuclear protein import, Ran GTPase, nuclear pore complex, nuclear import receptor, molecular recognition, nuclear transport
- MeSH terms
- Animals, Cell Nucleus, Models, Molecular, Nuclear Proteins, ran GTP-Binding Protein, Protein Transport, Active Transport, Cell Nucleus, Nuclear Pore Complex Proteins
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