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PMID: 19167330 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells.

Cell ·Vol. 136 ·No. 2 ·2009-01-23 ·Pages 284-95

D'Angelo MA, Raices M, Panowski SH, Hetzer MW

Abstract

In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of NPC components, like Nup153 and Nup50, are continuously exchanged, scaffold nucleoporins, like the Nup107/160 complex, are extremely long-lived and remain incorporated in the nuclear membrane during the entire cellular life span. Besides the lack of nucleoporin expression and NPC turnover, we discovered an age-related deterioration of NPCs, leading to an increase in nuclear permeability and the leaking of cytoplasmic proteins into the nucleus. Our finding that nuclear "leakiness" is dramatically accelerated during aging and that a subset of nucleoporins is oxidatively damaged in old cells suggests that the accumulation of damage at the NPC might be a crucial aging event.

MeSH Terms
Animals Caenorhabditis elegans Cell Nucleus/physiology Down-Regulation Mice Mitosis Nuclear Pore/physiology Nuclear Pore Complex Proteins/physiology Rats
Chemicals
Nuclear Pore Complex Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
D'Angelo Maximiliano A
Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Raices Marcela
Panowski Siler H
Hetzer Martin W
References (53)
53 references, click to expand
  1. Isolation and fractionation of rat brain nuclei.
    J Cell Biol. 1966 Aug;30(2):405-15 PMID: 5968977
  2. Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle.
    Cell. 2003 Feb 21;112(4):441-51 PMID: 12600309
  3. Removal of a single pore subcomplex results in vertebrate nuclei devoid of nuclear pores.
    Mol Cell. 2003 Apr;11(4):853-64 PMID: 12718872
  4. Timing requirements for insulin/IGF-1 signaling in C. elegans.
    Science. 2002 Oct 25;298(5594):830-4 PMID: 12399591
  5. The molecular architecture of the nuclear pore complex.
    Nature. 2007 Nov 29;450(7170):695-701 PMID: 18046406
  6. Remodelling the walls of the nucleus.
    Nat Rev Mol Cell Biol. 2002 Jul;3(7):487-97 PMID: 12094215
  7. The integral membrane nucleoporin pom121 functionally links nuclear pore complex assembly and nuclear envelope formation.
    Mol Cell. 2005 Jan 7;17(1):83-92 PMID: 15629719
  8. The role of the nuclear envelope in cellular organization.
    Cell Mol Life Sci. 2006 Feb;63(3):316-32 PMID: 16389459
  9. The genetics of Caenorhabditis elegans.
    Genetics. 1974 May;77(1):71-94 PMID: 4366476
  10. The conserved Nup107-160 complex is critical for nuclear pore complex assembly.
    Cell. 2003 Apr 18;113(2):195-206 PMID: 12705868
  11. Monitoring the permeability of the nuclear envelope during the cell cycle.
    Methods. 2006 Jan;38(1):17-24 PMID: 16343937
  12. Characterization of a germ-line proliferation mutation in C. elegans.
    Development. 1992 Nov;116(3):755-66 PMID: 1289064
  13. Correlation between structure and mass distribution of the nuclear pore complex and of distinct pore complex components.
    J Cell Biol. 1990 Apr;110(4):883-94 PMID: 2324201
  14. Age-related changes of nuclear architecture in Caenorhabditis elegans.
    Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16690-5 PMID: 16269543
  15. Histone turnover within nonproliferating cells.
    Proc Natl Acad Sci U S A. 1982 Feb;79(4):1163-5 PMID: 6951165
  16. Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan.
    Aging Cell. 2007 Aug;6(4):489-503 PMID: 17608836
  17. Yeast nuclear pore complexes have a cytoplasmic ring and internal filaments.
    J Struct Biol. 2004 Mar;145(3):272-88 PMID: 14960378
  18. Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins.
    Oncogene. 2006 Aug 28;25(38):5277-85 PMID: 16936748
  19. Oxidative modification of proteins: age-related changes.
    Gerontology. 2007;53(3):128-39 PMID: 17164550
  20. Time sequence of nuclear pore formation in phytohemagglutinin-stimulated lymphocytes and in HeLa cells during the cell cycle.
    J Cell Biol. 1972 Nov;55(2):433-47 PMID: 5076782
  21. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network.
    Cell. 2006 Aug 25;126(4):789-99 PMID: 16923397
  22. Cellular analyses of the mitotic region in the Caenorhabditis elegans adult germ line.
    Mol Biol Cell. 2006 Jul;17(7):3051-61 PMID: 16672375
  23. Nuclear envelope breakdown in starfish oocytes proceeds by partial NPC disassembly followed by a rapidly spreading fenestration of nuclear membranes.
    J Cell Biol. 2003 Mar 31;160(7):1055-68 PMID: 12654902
  24. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans.
    FASEB J. 1999 Aug;13(11):1385-93 PMID: 10428762
  25. An evolutionarily conserved NPC subcomplex, which redistributes in part to kinetochores in mammalian cells.
    J Cell Biol. 2001 Sep 17;154(6):1147-60 PMID: 11564755
  26. A C. elegans mutant that lives twice as long as wild type.
    Nature. 1993 Dec 2;366(6454):461-4 PMID: 8247153
  27. Protein carbonylation, cellular dysfunction, and disease progression.
    J Cell Mol Med. 2006 Apr-Jun;10(2):389-406 PMID: 16796807
  28. Caenorhabditis elegans nucleoporins Nup93 and Nup205 determine the limit of nuclear pore complex size exclusion in vivo.
    Mol Biol Cell. 2003 Dec;14(12):5104-15 PMID: 12937276
  29. Uncoupling of longevity and telomere length in C. elegans.
    PLoS Genet. 2005 Sep;1(3):e30 PMID: 16151516
  30. Mapping the dynamic organization of the nuclear pore complex inside single living cells.
    Nat Cell Biol. 2004 Nov;6(11):1114-21 PMID: 15502822
  31. Tpr is localized within the nuclear basket of the pore complex and has a role in nuclear protein export.
    J Cell Biol. 2002 Feb 18;156(4):617-30 PMID: 11839768
  32. Lamin A-dependent nuclear defects in human aging.
    Science. 2006 May 19;312(5776):1059-63 PMID: 16645051
  33. Nucleoporins as components of the nuclear pore complex core structure and Tpr as the architectural element of the nuclear basket.
    Mol Biol Cell. 2004 Sep;15(9):4261-77 PMID: 15229283
  34. Nuclear pore complex contains a family of glycoproteins that includes p62: glycosylation through a previously unidentified cellular pathway.
    Proc Natl Acad Sci U S A. 1987 Nov;84(21):7552-6 PMID: 3313397
  35. Specific in vivo roles for E2Fs in differentiation and development.
    Cell Cycle. 2007 Dec 1;6(23):2917-27 PMID: 17993781
  36. Asymmetric inheritance of oxidatively damaged proteins during cytokinesis.
    Science. 2003 Mar 14;299(5613):1751-3 PMID: 12610228
  37. Nup93, a vertebrate homologue of yeast Nic96p, forms a complex with a novel 205-kDa protein and is required for correct nuclear pore assembly.
    Mol Biol Cell. 1997 Oct;8(10):2017-38 PMID: 9348540
  38. Nuclear pores form de novo from both sides of the nuclear envelope.
    Science. 2006 Apr 21;312(5772):440-3 PMID: 16627745
  39. Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress.
    Neuropathol Appl Neurobiol. 2007 Feb;33(1):2-42 PMID: 17239006
  40. Oxidative stress causes abnormal accumulation of familial amyotrophic lateral sclerosis-related mutant SOD1 in transgenic Caenorhabditis elegans.
    Hum Mol Genet. 2001 Sep 15;10(19):2013-23 PMID: 11590119
  41. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans.
    Genes Dev. 2001 Oct 15;15(20):2654-9 PMID: 11641272
  42. Causes of oxidative stress in Alzheimer disease.
    Cell Mol Life Sci. 2007 Sep;64(17):2202-10 PMID: 17605000
  43. PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans.
    Nature. 2007 May 31;447(7144):550-5 PMID: 17476212
  44. Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells.
    J Cell Biol. 2001 Jul 9;154(1):71-84 PMID: 11448991
  45. The Sec13p complex and reconstitution of vesicle budding from the ER with purified cytosolic proteins.
    EMBO J. 1993 Nov;12(11):4073-82 PMID: 8223424
  46. The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex assembly in vertebrate cells.
    Mol Cell. 2006 Apr 7;22(1):93-103 PMID: 16600873
  47. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans.
    Science. 1997 Aug 15;277(5328):942-6 PMID: 9252323
  48. Nuclear pore complex structure and dynamics revealed by cryoelectron tomography.
    Science. 2004 Nov 19;306(5700):1387-90 PMID: 15514115
  49. Sequential recruitment of NPC proteins to the nuclear periphery at the end of mitosis.
    J Cell Sci. 1999 Jul;112 ( Pt 13):2253-64 PMID: 10362555
  50. Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span.
    Cell. 1998 Oct 16;95(2):199-210 PMID: 9790527
  51. A mechanism for asymmetric segregation of age during yeast budding.
    Nature. 2008 Aug 7;454(7205):728-34 PMID: 18660802
  52. Dynamics of nuclear pore complex organization through the cell cycle.
    Curr Opin Cell Biol. 2004 Jun;16(3):314-21 PMID: 15145357
  53. Oxidative and nitrative protein modifications in Parkinson's disease.
    Free Radic Biol Med. 2008 May 15;44(10):1787-94 PMID: 18395015
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.11.037
Published
2009-01-23
Pages
284-95
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2805151
Subset
IM
Grants
NIGMS NIH HHS · R01 GM057438 · United States
NIGMS NIH HHS · R01 GM057438-11 · United States
Corrections
CommentIn
PMID: 19167324
External Links
PubMed source DOI: 10.1016/j.cell.2008.11.037 PMC Full Text View journal details
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