POM121 and gp210 were, until this point, the only known membrane-integral nucleoporins (Nups) of vertebrates and, thus, the only candidate anchors for nuclear pore complexes (NPCs) within the nuclear membrane. In an accompanying study (see Stavru et al. on p. 477 of this issue), we provided evidence that NPCs can exist independently of POM121 and gp210, and we predicted that vertebrate NPCs contain additional membrane-integral constituents. We identify such an additional membrane protein in the NPCs of mammals, frogs, insects, and nematodes as the orthologue to yeast Ndc1p/Cut11p. Human NDC1 (hNDC1) likely possesses six transmembrane segments, and it is located at the nuclear pore wall. Depletion of hNDC1 from human HeLa cells interferes with the assembly of phenylalanine-glycine repeat Nups into NPCs. The loss of NDC1 function in Caenorhabditis elegans also causes severe NPC defects and very high larval and embryonic mortality. However, it is not ultimately lethal. Instead, homozygous NDC1-deficient worms can be propagated. This indicates that none of the membrane-integral Nups is universally essential for NPC assembly, and suggests that NPC biogenesis is an extremely fault-tolerant process.
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22 May 2006
Article|
May 15 2006
NDC1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes
Fabrizia Stavru,
Fabrizia Stavru
1Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany
2Max-Planck-Institut für Biophysikalische Chemie, D-37077 Göttingen, Germany
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Bastian B. Hülsmann,
Bastian B. Hülsmann
1Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany
2Max-Planck-Institut für Biophysikalische Chemie, D-37077 Göttingen, Germany
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Anne Spang,
Anne Spang
3Friedrich Miescher Laboratorium, Max-Planck-Gesellschaft, D-72076 Tübingen, Germany
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Enno Hartmann,
Enno Hartmann
4Institut für Biologie, Universität Lübeck, D-23538 Lübeck, Germany
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Volker C. Cordes,
Volker C. Cordes
1Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany
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Dirk Görlich
Dirk Görlich
1Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany
2Max-Planck-Institut für Biophysikalische Chemie, D-37077 Göttingen, Germany
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Fabrizia Stavru
1Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany
2Max-Planck-Institut für Biophysikalische Chemie, D-37077 Göttingen, Germany
Bastian B. Hülsmann
1Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany
2Max-Planck-Institut für Biophysikalische Chemie, D-37077 Göttingen, Germany
Anne Spang
3Friedrich Miescher Laboratorium, Max-Planck-Gesellschaft, D-72076 Tübingen, Germany
Enno Hartmann
4Institut für Biologie, Universität Lübeck, D-23538 Lübeck, Germany
Volker C. Cordes
1Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany
Dirk Görlich
1Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany
2Max-Planck-Institut für Biophysikalische Chemie, D-37077 Göttingen, Germany
Correspondence to Dirk Görlich: [email protected]
F. Stavru, B.B. Hülsmann, and A. Spang contributed equally to this paper.
A. Spang's present address is Biozentrum, Universität Basel, CH-4056 Basel, Switzerland.
Abbreviations used in this paper: FG, phenylalanine-glycine; INM, inner nuclear membrane; NE, nuclear envelope; NGS, N-glycosylation site; NPC, nuclear pore complex; Nup, nucleoporin; ONM, outer nuclear membrane; SPB, spindle pole body; TMS, transmembrane segment.
Received:
January 02 2006
Accepted:
April 18 2006
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 173 (4): 509–519.
Article history
Received:
January 02 2006
Accepted:
April 18 2006
Citation
Fabrizia Stavru, Bastian B. Hülsmann, Anne Spang, Enno Hartmann, Volker C. Cordes, Dirk Görlich; NDC1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes . J Cell Biol 22 May 2006; 173 (4): 509–519. doi: https://doi.org/10.1083/jcb.200601001
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