The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope
Abstract
The nuclear pore complex (NPC) consists of approximately 30 different proteins and provides the only sites for macromolecular transport between cytoplasm and nucleus. ALADIN was discovered as a new member of the NPC. Mutations in ALADIN are known to cause triple A syndrome, a rare autosomal recessive disorder characterized by adrenal insufficiency, alacrima, and achalasia. The function and exact location of the nucleoporin ALADIN within the NPC multiprotein complex is still unclear. Using a siRNA-based approach we downregulated the three known membrane integrated nucleoporins NDC1, GP210, and POM121 in stably expressing GFP-ALADIN HeLa cells. We identified NDC1 but not GP210 and POM121 as the main anchor of ALADIN within the NPC. Solely the depletion of NDC1 caused mislocalization of ALADIN. Vice versa, the depletion of ALADIN led also to disappearance of NDC1 at the NPC. However, the downregulation of two further membrane-integral nucleoporins GP210 and POM121 had no effect on ALADIN localization. Furthermore, we could show a direct association of NDC1 and ALADIN in NPCs by fluorescence resonance energy transfer (FRET) measurements. Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated. The loss of integration of ALADIN in the NPC is a main pathogenetic aspect for the development of the triple A syndrome and suggests that the interaction between ALADIN and NDC1 may be involved in the pathogenesis of the disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NDC1 interacts with the scaffold Nup Aladin.
“NDC1 is known to interact with the poorly characterized scaffold Nup Aladin (41,42).”
From AI-based structure prediction empowers integrative structural analysis of human nuclear pores (2022) · cites this paper as [42]
Cites
Zwischenmolekulare Energiewanderung und Fluoreszenz
Förster, T. (1948) · Annalen der Physik · doi:10.1002/andp.19484370105 · Cited by 8,285 · see citing works
Proteomic analysis of the mammalian nuclear pore complex
Cronshaw, J. M., Krutchinsky, A. N., Zhang, W., Chait, B. T., & Matunis, M. J. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200206106 · Cited by 968 · see citing works
A transient three-plasmid expression system for the production of high titer retroviral vectors
Soneoka, Y., Cannon, P. M., Ramsdale, E. E., Griffiths, J. C., Romano, G., Kingsman, S. M., & Kingsman, A. J. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.4.628 · Cited by 690 · see citing works
Demaison, C., Parsley, K. L., Brouns, G. S., Scherr, M., Battmer, K., Kinnon, C., Grez, M., & Thrasher, A. J. (2002) · Human Gene Therapy · doi:10.1089/10430340252898984 · Cited by 477 · see citing works
Mapping the dynamic organization of the nuclear pore complex inside single living cells
Rabut, G. E. E., Doye, V., & Ellenberg, J. (2004) · Nature Cell Biology · doi:10.1038/ncb1184 · Cited by 476 · see citing works
Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production
Allgrove, J., Clayden, G. S., Grant, D. B., & Macaulay, J. C. (1978) · The Lancet · doi:10.1016/s0140-6736(78)91268-0 · Cited by 448 · see citing works
The nuclear pore complex: nucleocytoplasmic transport and beyond
Fahrenkrog, B., & Aebi, U. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1230 · Cited by 421 · see citing works
Mutant WD-repeat protein in triple-A syndrome
Tullio-Pelet, A., Salomon, R., Hadj-Rabia, S., Mugnier, C., de Laet, M.-H., Chaouachi, B., Bakiri, F., Brottier, P., Cattolico, L., Penet, C., et al. (2000) · Nature Genetics · doi:10.1038/81642 · Cited by 312 · see citing works
Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene
Handschug, K. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.3.283 · Cited by 257 · see citing works
Mansfeld, J., Güttinger, S., Hawryluk-Gara, L. A., Panté, N., Mall, M., Galy, V., Haselmann, U., Mühlhäusser, P., Wozniak, R. W., Mattaj, I. W., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.015 · Cited by 221 · see citing works
NDC1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes
Stavru, F., Hülsmann, B. B., Spang, A., Hartmann, E., Cordes, V. C., & Görlich, D. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200601001 · Cited by 174 · see citing works
The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome
Cronshaw, J. M., & Matunis, M. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1031047100 · Cited by 173 · see citing works
Gazarian, M., Cowell, C., Bonney, M., & Grigor, W. G. (1995) · European Journal of Pediatrics · doi:10.1007/bf01972967 · Cited by 134 · see citing works
Bapteste, E., Charlebois, R. L., MacLeod, D., & Brochier, C. (2005) · Genome Biology · doi:10.1186/gb-2005-6-10-r85 · Cited by 89 · see citing works
The nuclear pore complex: disease associations and functional correlations
Cronshaw, J. M., & Matunis, M. J. (2003) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2003.11.005 · Cited by 78 · see citing works
Huebner, A., Elias, L. L. K., & Clark, A. J. L. (1999) · PubMed · Cited by 69 · see citing works
Self-citationKrumbholz, M., Koehler, K., & Huebner, A. (2006) · Biochemistry and Cell Biology · doi:10.1139/o05-198 · Cited by 66 · see citing works
Self-citationMoreno-Carranza, B., Gentsch, M., Stein, S., Schambach, A., Santilli, G., Rudolf, E., Ryser, M., Haria, S., Thrasher, A., Baum, C., et al. (2009) · Gene Therapy · doi:10.1038/gt.2008.143 · Cited by 63 · see citing works
Visualizing protein–RNA interactions inside cells by fluorescence resonance energy transfer
Lorenz, M. (2008) · RNA · doi:10.1261/rna.1307809 · Cited by 45 · see citing works
Self-citationThe transmembrane nucleoporin NDC1 is required for targeting of ALADIN to nuclear pore complexes
Yamazumi, Y., Kamiya, A., Nishida, A., Nishihara, A., Iemura, S.-I., Natsume, T., & Akiyama, T. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.08.096 · Cited by 34 · see citing works
Koehler, K., Brockmann, K., Krumbholz, M., et al. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.132 · Cited by 27 · see citing works
Self-citationTsigos, C., & Chrousos, G. P. (1998) · Humana Press eBooks · doi:10.1007/978-1-4612-1802-9_15 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
AI-based structure prediction empowers integrative structural analysis of human nuclear pores
Mosalaganti, S., Obarska-Kosinska, A., Siggel, M., Taniguchi, R., Turoňová, B., Zimmerli, C. E., Buczak, K., Schmidt, F. H., Margiotta, E., Mackmull, M.-T., et al. (2022) · Science · doi:10.1126/science.abm9506 · Cited by 355 · see citing works
- Authors
- Kind, B., Koehler, K., Lorenz, M., & Huebner, A.
- Affiliations
- Technische Universität Dresden (DE)
- Max Planck Society (DE)
- Corresponding author
- Huebner, Angela
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 390
- Issue
- 2
- Pages
- 205-210
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1993539744
- Cited by
- 48
- References
- 22
- Citations by year
- 2024: 4 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 1 · 2013: 2 · 2012: 5
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (DFG, HU395)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- ALADIN, nuclear pore complex, NDC1, POM121, gp210, nucleoporins, triple A syndrome, protein-protein interaction, nuclear transport, protein mislocalization
- MeSH terms
- HeLa Cells, Humans, Membrane Glycoproteins, Nerve Tissue Proteins, Nuclear Envelope, Nuclear Pore Complex Proteins, Gene Knockdown Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
