Advertisement

Histochemistry and Cell Biology

, Volume 150, Issue 6, pp 593–605 | Cite as

Moonlighting nuclear pore proteins: tissue-specific nucleoporin function in health and disease

  • Ramona Jühlen
  • Birthe FahrenkrogEmail author
Review

Abstract

The nuclear pore complex is the main transportation hub for exchange between the cytoplasm and the nucleus. It is built from nucleoporins that form distinct subcomplexes to establish this huge protein complex in the nuclear envelope. Malfunctioning of nucleoporins is well known in human malignancies, such as gene fusions of NUP214 and NUP98 in hematological neoplasms and overexpression of NUP88 in a variety of human cancers. In the past decade, the incremental utilization of next-generation sequencing has unraveled mutations in nucleoporin genes in the context of an increasing number of hereditary diseases, often in a tissue-specific manner. It emerges that, on one hand, the central nervous system and the heart are particularly sensitive to mutations in nucleoporin genes. On the other hand, nucleoporins forming the scaffold structure of the nuclear pore complex are eminently mutation-prone. These novel and exciting associations between nucleoporins and human diseases emphasize the need to shed light on these unanticipated tissue-specific roles of nucleoporins that may go well beyond their role in nucleocytoplasmic transport. In this review, the current insights into altered nucleoporin function associated with human hereditary disorders will be discussed.

Keywords

Cellular stress Neurodegeneration Nuclear pore complex Nucleocytoplasmic transport Nucleoporins Whole-exome sequencing 

Notes

Acknowledgements

This work was supported by a Grant from the Fédération Wallonie-Bruxelles (ARC 4.110.F.000092F).

References

  1. Abramson J, Giraud M, Benoist C, Mathis D (2010) Aire’s partners in the molecular control of immunological tolerance. Cell 140:123–135.  https://doi.org/10.1016/j.cell.2009.12.030 CrossRefPubMedGoogle Scholar
  2. Aditi GL, Dawson TR, Wente SR (2016) An amyotrophic lateral sclerosis-linked mutation in GLE1 alters the cellular pool of human Gle1 functional isoforms. Adv Biol Regul 62:25–36.  https://doi.org/10.1016/j.jbior.2015.11.001 CrossRefPubMedGoogle Scholar
  3. Alanee S, Delfino K, Wilber A et al (2017) Single nucleotide variant in Nucleoporin 107 may be predictive of sensitivity to chemotherapy in patients with ovarian cancer. Pharmacogenet Genomics 27:264–269.  https://doi.org/10.1097/FPC.0000000000000288 CrossRefPubMedGoogle Scholar
  4. Alazami AM, Patel N, Shamseldin HE et al (2015) Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. Cell Rep 10:148–161.  https://doi.org/10.1016/j.celrep.2014.12.015 CrossRefPubMedGoogle Scholar
  5. Albagha OME, Wani SE, Visconti MR et al (2011) Genome-wide association identifies three new susceptibility loci for Paget’s disease of bone. Nat Genet 43:685–689.  https://doi.org/10.1038/ng.845 CrossRefPubMedGoogle Scholar
  6. Aslanukov A, Bhowmick R, Guruju M et al (2006) RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism. PLoS Genet 2:e177.  https://doi.org/10.1371/journal.pgen.0020177 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Basel-Vanagaite L, Muncher L, Straussberg R et al (2006) Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis. Ann Neurol 60:214–222.  https://doi.org/10.1002/ana.20902 CrossRefPubMedGoogle Scholar
  8. Bastos R, Ribas de Pouplana L, Enarson M et al (1997) Nup84, a novel nucleoporin that is associated with CAN/Nup214 on the cytoplasmic face of the nuclear pore complex. J Cell Biol 137:989–1000CrossRefGoogle Scholar
  9. Beck M, Forster F, Ecke M et al (2004) Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science 306:1387–1390CrossRefGoogle Scholar
  10. Beecroft SJ, Lombard M, Mowat D et al (2018) Genetics of neuromuscular fetal akinesia in the genomics era. J Med Genet 55:505–514.  https://doi.org/10.1136/jmedgenet-2018-105266 CrossRefPubMedGoogle Scholar
  11. Belgareh N, Rabut G, Baï SW et al (2001) An evolutionarily conserved NPC subcomplex, which redistributes in part to kinetochores in mammalian cells. J Cell Biol 154:1147–1160.  https://doi.org/10.1083/jcb.200101081 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bergamino L, Capra V, Biancheri R et al (2012) Immunomodulatory therapy in recurrent acute necrotizing encephalopathy ANE1: Is it useful? Brain Dev 34:384–391.  https://doi.org/10.1016/j.braindev.2011.08.001 CrossRefPubMedGoogle Scholar
  13. Bischoff FR, Krebber H, Kempf T et al (1995) Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport. Proc Natl Acad Sci USA 92:1749–1753CrossRefGoogle Scholar
  14. Bloch C, Suter B, Fischmann A et al (2015) Only a touch of the flu? The simultaneous manifestation of acute necrotizing encephalopathy in two consanguineous patients. Open Forum Infect Dis 2:ofv013.  https://doi.org/10.1093/ofid/ofv013 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Bonnin E, Cabochette P, Filosa A et al (2018) Mutations in nucleoporin NUP88 cause lethal fetal akinesia deformation sequence. bioRxiv.  https://doi.org/10.1101/347179 CrossRefGoogle Scholar
  16. Braun DA, Sadowski CE, Kohl S et al (2016) Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. Nat Genet 48:457–465.  https://doi.org/10.1038/ng.3512 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Breslow DK, Koslover EF, Seydel F et al (2013) An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier. J Cell Biol 203:129–147.  https://doi.org/10.1083/jcb.201212024 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Brownawell AM, Macara IG (2002) Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding proteins. J Cell Biol 156:53–64.  https://doi.org/10.1083/jcb.200110082 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Bui KH, von Appen A, DiGuilio AL et al (2013) Integrated structural analysis of the human nuclear pore complex scaffold. Cell 155:1233–1243.  https://doi.org/10.1016/j.cell.2013.10.055 CrossRefPubMedGoogle Scholar
  20. Bullock TL, Clarkson WD, Kent HM, Stewart M (1996) The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2). J Mol Biol 260:422–431CrossRefGoogle Scholar
  21. Capelson M, Doucet C, Hetzer MW (2010) Nuclear pore complexes: guardians of the nuclear genome. Cold Spring Harb Symp Quant Biol 75:585–597.  https://doi.org/10.1101/sqb.2010.75.059 CrossRefPubMedGoogle Scholar
  22. Chang W-L, Tarn W-Y (2009) A role for transportin in deposition of TTP to cytoplasmic RNA granules and mRNA decay. Nucleic Acids Res 37:6600–6612.  https://doi.org/10.1093/nar/gkp717 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Cho K-I, Yoon D, Qiu S et al (2017) Loss of Ranbp2 in motoneurons causes disruption of nucleocytoplasmic and chemokine signaling, proteostasis of hnRNPH3 and Mmp28, and development of amyotrophic lateral sclerosis-like syndromes. Dis Model Mech 10:559–579.  https://doi.org/10.1242/dmm.027730 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Cortés R, Roselló-Lletí E, Rivera M et al (2010) Influence of heart failure on nucleocytoplasmic transport in human cardiomyocytes. Cardiovasc Res 85:464–472.  https://doi.org/10.1093/cvr/cvp336 CrossRefPubMedGoogle Scholar
  25. Cronshaw JM, Matunis MJ (2004) The nuclear pore complex: disease associations and functional correlations. Trends Endocrinol Metab TEM 15:34–39CrossRefGoogle Scholar
  26. Cronshaw JM, Krutchinsky AN, Zhang W et al (2002) Proteomic analysis of the mammalian nuclear pore complex. J Cell Biol 158:915–927.  https://doi.org/10.1083/jcb.200206106 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Dargemont C, Schmidt-Zachmann MS, Kühn LC (1995) Direct interaction of nucleoporin p62 with mRNA during its export from the nucleus. J Cell Sci 108(Pt 1):257–263PubMedGoogle Scholar
  28. Del Viso F, Huang F, Myers J et al (2016) Congenital heart disease genetics uncovers context-dependent organization and function of nucleoporins at Cilia. Dev Cell 38:478–492.  https://doi.org/10.1016/j.devcel.2016.08.002 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Denier C, Balu L, Husson B et al (2014) Familial acute necrotizing encephalopathy due to mutation in the RANBP2 gene. J Neurol Sci 345:236–238.  https://doi.org/10.1016/j.jns.2014.07.025 CrossRefPubMedGoogle Scholar
  30. Devos D, Dokudovskaya S, Williams R et al (2006) Simple fold composition and modular architecture of the nuclear pore complex. Proc Natl Acad Sci USA 103:2172–2177CrossRefGoogle Scholar
  31. Egloff M, Nguyen L-S, Siquier-Pernet K et al (2018) Whole-exome sequence analysis highlights the role of unmasked recessive mutations in copy number variants with incomplete penetrance. Eur J Hum Genet EJHG 26:912–918.  https://doi.org/10.1038/s41431-018-0124-4 CrossRefPubMedGoogle Scholar
  32. Endicott SJ, Brueckner M (2018) NUP98 sets the size-exclusion diffusion limit through the ciliary base. Curr Biol CB 28:1643–1650.e3.  https://doi.org/10.1016/j.cub.2018.04.014 CrossRefPubMedGoogle Scholar
  33. Fakhro KA, Choi M, Ware SM et al (2011) Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning. Proc Natl Acad Sci USA 108:2915–2920.  https://doi.org/10.1073/pnas.1019645108 CrossRefPubMedGoogle Scholar
  34. Fan S, Margolis B (2011) The Ran importin system in cilia trafficking. Organogenesis 7:147–153.  https://doi.org/10.4161/org.7.3.17084 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Fan S, Whiteman EL, Hurd TW et al (2011) Induction of Ran GTP drives ciliogenesis. Mol Biol Cell 22:4539–4548.  https://doi.org/10.1091/mbc.E11-03-0267 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Feldherr CM, Akin D (1997) The location of the transport gate in the nuclear pore complex. J Cell Sci 110(Pt 24):3065–3070PubMedGoogle Scholar
  37. Finsterer J (2008) Leigh and Leigh-like syndrome in children and adults. Pediatr Neurol 39:223–235.  https://doi.org/10.1016/j.pediatrneurol.2008.07.013 CrossRefPubMedGoogle Scholar
  38. Fiserova J, Kiseleva E, Goldberg MW (2009) Nuclear envelope and nuclear pore complex structure and organization in tobacco BY-2 cells. Plant J Cell Mol Biol 59:243–255.  https://doi.org/10.1111/j.1365-313X.2009.03865.x CrossRefGoogle Scholar
  39. Folkmann AW, Dawson TR, Wente SR (2014) Insights into mRNA export-linked molecular mechanisms of human disease through a Gle1 structure-function analysis. Adv Biol Regul 54:74–91.  https://doi.org/10.1016/j.jbior.2013.10.002 CrossRefPubMedGoogle Scholar
  40. Fornerod M, van Deursen J, van Baal S et al (1997) The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88. EMBO J 16:807–816.  https://doi.org/10.1093/emboj/16.4.807 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Frenkiel-Krispin D, Maco B, Aebi U, Medalia O (2010) Structural analysis of a metazoan nuclear pore complex reveals a fused concentric ring architecture. J Mol Biol 395:578–586.  https://doi.org/10.1016/j.jmb.2009.11.010 CrossRefPubMedGoogle Scholar
  42. Fried H, Kutay U (2003) Nucleocytoplasmic transport: taking an inventory. Cell Mol Life Sci CMLS 60:1659–1688.  https://doi.org/10.1007/s00018-003-3070-3 CrossRefPubMedGoogle Scholar
  43. Fujimura K, Suzuki T, Yasuda Y et al (2010) Identification of importin α1 as a novel constituent of RNA stress granules. Biochim Biophys Acta BBA Mol Cell Res 1803:865–871.  https://doi.org/10.1016/j.bbamcr.2010.03.020 CrossRefGoogle Scholar
  44. Garg P (2018) A review of podocyte biology. Am J Nephrol 47:3–13.  https://doi.org/10.1159/000481633 CrossRefPubMedGoogle Scholar
  45. Gasset-Rosa F, Chillon-Marinas C, Goginashvili A et al (2017) Polyglutamine-expanded huntingtin exacerbates age-related disruption of nuclear integrity and nucleocytoplasmic transport. Neuron 94:48–57.e4.  https://doi.org/10.1016/j.neuron.2017.03.027 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Gika AD, Rich P, Gupta S et al (2010) Recurrent acute necrotizing encephalopathy following influenza A in a genetically predisposed family. Dev Med Child Neurol 52:99–102.  https://doi.org/10.1111/j.1469-8749.2009.03405.x CrossRefPubMedGoogle Scholar
  47. Grant DB, Dunger DB, Smith I, Hyland K (1992) Familial glucocorticoid deficiency with achalasia of the cardia associated with mixed neuropathy, long-tract degeneration and mild dementia. Eur J Pediatr 151:85–89CrossRefGoogle Scholar
  48. Griffis ER, Xu S, Powers MA (2003) Nup98 localizes to both nuclear and cytoplasmic sides of the nuclear pore and binds to two distinct nucleoporin subcomplexes. Mol Biol Cell 14:600–610.  https://doi.org/10.1091/mbc.e02-09-0582 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Grima JC, Daigle JG, Arbez N et al (2017) Mutant huntingtin disrupts the nuclear pore complex. Neuron 94:93–107.e6.  https://doi.org/10.1016/j.neuron.2017.03.023 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Habbig S, Liebau MC (2015) Ciliopathies—from rare inherited cystic kidney diseases to basic cellular function. Mol Cell Pediatr 2:8.  https://doi.org/10.1186/s40348-015-0019-1 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Handschug K, Sperling S, Yoon SJ et al (2001) Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Hum Mol Genet 10:283–290CrossRefGoogle Scholar
  52. Haskell GT, Jensen BC, Samsa LA et al (2017) Whole exome sequencing identifies truncating variants in nuclear envelope genes in patients with cardiovascular disease. Circ Cardiovasc Genet.  https://doi.org/10.1161/CIRCGENETICS.116.001443 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Hawryluk-Gara LA, Shibuya EK, Wozniak RW (2005) Vertebrate Nup53 interacts with the nuclear lamina and is required for the assembly of a Nup93-containing complex. Mol Biol Cell 16:2382–2394.  https://doi.org/10.1091/mbc.e04-10-0857 CrossRefPubMedPubMedCentralGoogle Scholar
  54. Hezwani M, Fahrenkrog B (2017) The functional versatility of the nuclear pore complex proteins. Semin Cell Dev Biol 68:2–9.  https://doi.org/10.1016/j.semcdb.2017.05.004 CrossRefPubMedGoogle Scholar
  55. Hill M (2003) The neuromuscular junction disorders. J Neurol Neurosurg Psychiatry 74:ii32–ii37.  https://doi.org/10.1136/jnnp.74.suppl_2.ii32 CrossRefPubMedPubMedCentralGoogle Scholar
  56. Hirano M, Furiya Y, Asai H et al (2006) ALADINI482S causes selective failure of nuclear protein import and hypersensitivity to oxidative stress in triple A syndrome. Proc Natl Acad Sci USA 103:2298–2303.  https://doi.org/10.1073/pnas.0505598103 CrossRefPubMedGoogle Scholar
  57. Howard A, Uyeki TM, Fergie J (2018) Influenza-associated acute necrotizing encephalopathy in siblings. J Pediatr Infect Dis Soc 7:e172–e177.  https://doi.org/10.1093/jpids/piy033 CrossRefGoogle Scholar
  58. Huberts DHEW, van der Klei IJ (2010) Moonlighting proteins: an intriguing mode of multitasking. Biochim Biophys Acta BBA Mol Cell Res 1803:520–525.  https://doi.org/10.1016/j.bbamcr.2010.01.022 CrossRefGoogle Scholar
  59. Huebner A, Mann P, Rohde E et al (2006) Mice lacking the nuclear pore complex protein ALADIN show female infertility but fail to develop a phenotype resembling human triple A syndrome. Mol Cell Biol 26:1879–1887.  https://doi.org/10.1128/MCB.26.5.1879-1887.2006 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Itoh G, Sugino S, Ikeda M et al (2013) Nucleoporin Nup188 is required for chromosome alignment in mitosis. Cancer Sci 104:871–879.  https://doi.org/10.1111/cas.12159 CrossRefPubMedGoogle Scholar
  61. Jäkel S, Mingot J-M, Schwarzmaier P et al (2002) Importins fulfil a dual function as nuclear import receptors and cytoplasmic chaperones for exposed basic domains. EMBO J 21:377–386.  https://doi.org/10.1093/emboj/21.3.377 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Jao L-E, Appel B, Wente SR (2012) A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization. Dev Camb Engl 139:1316–1326.  https://doi.org/10.1242/dev.074344 CrossRefGoogle Scholar
  63. Jao L-E, Akef A, Wente SR (2017) A role for Gle1, a regulator of DEAD-box RNA helicases, at centrosomes and basal bodies. Mol Biol Cell 28:120–127.  https://doi.org/10.1091/mbc.E16-09-0675 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Jeffery CJ (1999) Moonlighting proteins. Trends Biochem Sci 24:8–11.  https://doi.org/10.1016/S0968-0004(98)01335-8 CrossRefPubMedGoogle Scholar
  65. Jühlen R, Idkowiak J, Taylor AE et al (2015) Role of ALADIN in human adrenocortical cells for oxidative stress response and steroidogenesis. PloS One 10:e0124582.  https://doi.org/10.1371/journal.pone.0124582 CrossRefPubMedPubMedCentralGoogle Scholar
  66. Jühlen R, Peitzsch M, Gärtner S et al (2018) Compensation for chronic oxidative stress in ALADIN null mice. Biol Open.  https://doi.org/10.1242/bio.030742 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Kane M, Rebensburg SV, Takata MA et al (2018) Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2. eLife.  https://doi.org/10.7554/eLife.35738 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Kaneb HM, Folkmann AW, Belzil VV et al (2015) Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis. Hum Mol Genet 24:1363–1373.  https://doi.org/10.1093/hmg/ddu545 CrossRefPubMedGoogle Scholar
  69. Katsani KR, Irimia M, Karapiperis C et al (2014) Functional genomics evidence unearths new moonlighting roles of outer ring coat nucleoporins. Sci Rep 4:4655.  https://doi.org/10.1038/srep04655 CrossRefPubMedPubMedCentralGoogle Scholar
  70. Kee HL, Dishinger JF, Blasius TL et al (2012) A size-exclusion permeability barrier and nucleoporins characterize a ciliary pore complex that regulates transport into cilia. Nat Cell Biol 14:431–437.  https://doi.org/10.1038/ncb2450 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Kendirgi F, Rexer DJ, Alcázar-Román AR et al (2005) Interaction between the shuttling mRNA export factor Gle1 and the nucleoporin hCG1: a conserved mechanism in the export of Hsp70 mRNA. Mol Biol Cell 16:4304–4315.  https://doi.org/10.1091/mbc.E04-11-0998 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Kind B, Koehler K, Lorenz M, Huebner A (2009) The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope. Biochem Biophys Res Commun 390:205–210.  https://doi.org/10.1016/j.bbrc.2009.09.080 CrossRefPubMedGoogle Scholar
  73. Kind B, Koehler K, Krumbholz M et al (2010) Intracellular ROS level is increased in fibroblasts of triple A syndrome patients. J Mol Med 88:1233–1242.  https://doi.org/10.1007/s00109-010-0661-y;CrossRefPubMedGoogle Scholar
  74. Kinoshita Y, Ito H, Hirano A et al (2009) Nuclear contour irregularity and abnormal transporter protein distribution in anterior horn cells in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 68:1184–1192.  https://doi.org/10.1097/NEN.0b013e3181bc3bec CrossRefPubMedGoogle Scholar
  75. Kinoshita Y, Hunter RG, Gray JD et al (2014) Role for NUP62 depletion and PYK2 redistribution in dendritic retraction resulting from chronic stress. Proc Natl Acad Sci USA 111:16130–16135.  https://doi.org/10.1073/pnas.1418896111 CrossRefPubMedGoogle Scholar
  76. Kiseleva E, Allen TD, Rutherford S et al (2004) Yeast nuclear pore complexes have a cytoplasmic ring and internal filaments. J Struct Biol 145:272–288.  https://doi.org/10.1016/j.jsb.2003.11.010 CrossRefPubMedGoogle Scholar
  77. Koehler K, End K, Kind B et al (2013) Changes in differential gene expression in fibroblast cells from patients with triple A syndrome under oxidative stress. Horm Metab Res 45:102–108.  https://doi.org/10.1055/s-0032-1331196 CrossRefPubMedGoogle Scholar
  78. Korfali N, Wilkie GS, Swanson SK et al (2010) The leukocyte nuclear envelope proteome varies with cell activation and contains novel transmembrane proteins that affect genome architecture. Mol Cell Proteomics MCP 9:2571–2585.  https://doi.org/10.1074/mcp.M110.002915 CrossRefPubMedGoogle Scholar
  79. Krumbholz M, Koehler K, Huebner A (2006) Cellular localization of 17 natural mutant variants of ALADIN protein in triple A syndrome—shedding light on an unexpected splice mutation. Biochem Cell Biol 84:243–249.  https://doi.org/10.1139/o05-198 CrossRefPubMedGoogle Scholar
  80. Lee Y-J, Hwang S-K, Lee SM, Kwon S (2017) Familial acute necrotizing encephalopathy with RANBP2 mutation: the first report in Northeast Asia. Brain Dev 39:625–628.  https://doi.org/10.1016/j.braindev.2017.02.005 CrossRefPubMedGoogle Scholar
  81. Lemke EA (2016) The multiple faces of disordered nucleoporins. J Mol Biol 428:2011–2024.  https://doi.org/10.1016/j.jmb.2016.01.002 CrossRefPubMedGoogle Scholar
  82. Lima FA, Moreira-Filho CA, Ramos PL et al (2011) Decreased AIRE expression and global thymic hypofunction in Down syndrome. J Immunol Baltim Md 1950 187:3422–3430.  https://doi.org/10.4049/jimmunol.1003053 CrossRefGoogle Scholar
  83. Loh N-R, Appleton DB (2010) Untreated recurrent acute necrotising encephalopathy associated with RANBP2 mutation, and normal outcome in a Caucasian boy. Eur J Pediatr 169:1299–1302.  https://doi.org/10.1007/s00431-010-1213-8 CrossRefPubMedGoogle Scholar
  84. Lönnqvist T, Isohanni P, Valanne L et al (2011) Dominant encephalopathy mimicking mitochondrial disease. Neurology 76:101–103.  https://doi.org/10.1212/WNL.0b013e318203e908 CrossRefPubMedGoogle Scholar
  85. Lund E, Güttinger S, Calado A et al (2004) Nuclear export of microRNA precursors. Science 303:95–98.  https://doi.org/10.1126/science.1090599 CrossRefPubMedGoogle Scholar
  86. Mahboubi H, Seganathy E, Kong D, Stochaj U (2013) Identification of novel stress granule components that are involved in nuclear transport. PLOS One 8:e68356.  https://doi.org/10.1371/journal.pone.0068356 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Maimon T, Elad N, Dahan I, Medalia O (2012) The human nuclear pore complex as revealed by cryo-electron tomography. Struct Lond Engl 1993 20:998–1006.  https://doi.org/10.1016/j.str.2012.03.025 CrossRefGoogle Scholar
  88. Marco EJ, Anderson JE, Neilson DE, Strober JB (2010) Acute necrotizing encephalopathy in 3 brothers. Pediatrics 125:e693–e698.  https://doi.org/10.1542/peds.2009-1984 CrossRefPubMedPubMedCentralGoogle Scholar
  89. Miyake N, Tsukaguchi H, Koshimizu E et al (2015) Biallelic mutations in nuclear pore complex subunit NUP107 cause early-childhood-onset steroid-resistant nephrotic syndrome. Am J Hum Genet 97:555–566.  https://doi.org/10.1016/j.ajhg.2015.08.013 CrossRefPubMedPubMedCentralGoogle Scholar
  90. Naylor RM, Jeganathan KB, Cao X, van Deursen JM (2016) Nuclear pore protein NUP88 activates anaphase-promoting complex to promote aneuploidy. J Clin Invest 126:543–559.  https://doi.org/10.1172/JCI82277 CrossRefPubMedPubMedCentralGoogle Scholar
  91. Neilson DE, Adams MD, Orr CM et al (2009) Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2. Am J Hum Genet 84:44–51.  https://doi.org/10.1016/j.ajhg.2008.12.009 CrossRefPubMedPubMedCentralGoogle Scholar
  92. Nishimura N, Higuchi Y, Kimura N et al (2016) Familial acute necrotizing encephalopathy without RANBP2 mutation: poor outcome. Pediatr Int Off J Jpn Pediatr Soc 58:1215–1218.  https://doi.org/10.1111/ped.13119 CrossRefGoogle Scholar
  93. Nousiainen HO, Kestilä M, Pakkasjärvi N et al (2008) Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease. Nat Genet 40:155–157.  https://doi.org/10.1038/ng.2007.65 CrossRefPubMedPubMedCentralGoogle Scholar
  94. Ori A, Banterle N, Iskar M et al (2013) Cell type-specific nuclear pores: a case in point for context-dependent stoichiometry of molecular machines. Mol Syst Biol 9:648.  https://doi.org/10.1038/msb.2013.4 CrossRefPubMedPubMedCentralGoogle Scholar
  95. Pante N, Kann M (2002) Nuclear pore complex is able to transport macromolecules with diameters of about 39 nm. Mol Biol Cell 13:425–434.  https://doi.org/10.1091/mbc.01-06-0308 CrossRefPubMedPubMedCentralGoogle Scholar
  96. Parish IA, Stamp LA, Lorenzo AMD et al (2016) A novel mutation in nucleoporin 35 causes murine degenerative colonic smooth muscle myopathy. Am J Pathol 186:2254–2261.  https://doi.org/10.1016/j.ajpath.2016.04.016 CrossRefPubMedPubMedCentralGoogle Scholar
  97. Park E, Ahn YH, Kang HG et al (2017) NUP107 mutations in children with steroid-resistant nephrotic syndrome. Nephrol Dial Transpl Off Publ Eur Dial Transpl Assoc Eur Ren Assoc 32:1013–1017.  https://doi.org/10.1093/ndt/gfw103 CrossRefGoogle Scholar
  98. Percipalle P, Clarkson WD, Kent HM et al (1997) Molecular interactions between the importin α/β heterodimer and proteins involved in vertebrate nuclear protein import 11 edited J. Karn. J Mol Biol 266:722–732.  https://doi.org/10.1006/jmbi.1996.0801 CrossRefPubMedGoogle Scholar
  99. Piatigorsky J, Wistow GJ (1989) Enzyme/crystallins: gene sharing as an evolutionary strategy. Cell 57:197–199.  https://doi.org/10.1016/0092-8674(89)90956-2 CrossRefPubMedGoogle Scholar
  100. Pichler A, Gast A, Seeler JS et al (2002) The nucleoporin RanBP2 has SUMO1 E3 ligase activity. Cell 108:109–120CrossRefGoogle Scholar
  101. Prasad R, Metherell LA, Clark AJ, Storr HL (2013) Deficiency of ALADIN impairs redox homeostasis in human adrenal cells and inhibits steroidogenesis. Endocrinology 154:3209–3218.  https://doi.org/10.1210/en.2013-1241 CrossRefPubMedPubMedCentralGoogle Scholar
  102. Ravenscroft G, Sollis E, Charles AK et al (2011) Fetal akinesia: review of the genetics of the neuromuscular causes. J Med Genet 48:793–801.  https://doi.org/10.1136/jmedgenet-2011-100211 CrossRefPubMedGoogle Scholar
  103. Rayala HJ, Kendirgi F, Barry DM et al (2004) The mRNA export factor human Gle1 interacts with the nuclear pore complex protein Nup155. Mol Cell Proteomics MCP 3:145–155.  https://doi.org/10.1074/mcp.M300106-MCP200 CrossRefPubMedGoogle Scholar
  104. Reichelt R, Holzenburg A, Buhle EL Jr et al (1990) Correlation between structure and mass distribution of the nuclear pore complex and of distinct pore complex components. J Cell Biol 110:883–894CrossRefGoogle Scholar
  105. Reiter JF, Leroux MR (2017) Genes and molecular pathways underpinning ciliopathies. Nat Rev Mol Cell Biol 18:533–547.  https://doi.org/10.1038/nrm.2017.60 CrossRefPubMedPubMedCentralGoogle Scholar
  106. Ren Y, Diao F, Katari S et al (2018) Functional study of a novel missense single-nucleotide variant of NUP107 in two daughters of Mexican origin with premature ovarian insufficiency. Mol Genet Genomic Med 6:276–281.  https://doi.org/10.1002/mgg3.345 CrossRefPubMedPubMedCentralGoogle Scholar
  107. Rosti RO, Sotak BN, Bielas SL et al (2017) Homozygous mutation in NUP107 leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway–Mowat syndrome. J Med Genet 54:399–403.  https://doi.org/10.1136/jmedgenet-2016-104237 CrossRefPubMedGoogle Scholar
  108. Rout MP, Aitchison JD, Suprapto A et al (2000) The yeast nuclear pore complex: composition, architecture, and transport mechanism. J Cell Biol 148:635–651CrossRefGoogle Scholar
  109. Ryan KJ, White CC, Patel K et al (2017) A human microglia-like cellular model for assessing the effects of neurodegenerative disease gene variants. Sci Transl Med.  https://doi.org/10.1126/scitranslmed.aai7635 CrossRefPubMedPubMedCentralGoogle Scholar
  110. Satoh M, Akatsu T, Ishkawa Y et al (2007) A novel activator of C-C chemokine, FROUNT, is expressed with C-C chemokine receptor 2 and its ligand in failing human heart. J Card Fail 13:114–119.  https://doi.org/10.1016/j.cardfail.2006.11.003 CrossRefPubMedGoogle Scholar
  111. Schwartz TU (2005) Modularity within the architecture of the nuclear pore complex. Curr Opin Struct Biol 15:221–226CrossRefGoogle Scholar
  112. Schwartz TU (2016) The structure inventory of the nuclear pore complex. J Mol Biol 428:1986–2000.  https://doi.org/10.1016/j.jmb.2016.03.015 CrossRefPubMedPubMedCentralGoogle Scholar
  113. Sell K, Storch K, Hahn G et al (2016) Variable clinical course in acute necrotizing encephalopathy and identification of a novel RANBP2 mutation. Brain Dev 38:777–780.  https://doi.org/10.1016/j.braindev.2016.02.007 CrossRefPubMedGoogle Scholar
  114. Seytanoglu A, Alsomali NI, Valori CF et al (2016) Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo. Neuroscience 322:287–297.  https://doi.org/10.1016/j.neuroscience.2016.02.039 CrossRefPubMedGoogle Scholar
  115. Sheffield LG, Miskiewicz HB, Tannenbaum LB, Mirra SS (2006) Nuclear pore complex proteins in Alzheimer disease. J Neuropathol Exp Neurol 65:45–54CrossRefGoogle Scholar
  116. Singh RR, Sedani S, Lim M et al (2015) RANBP2 mutation and acute necrotizing encephalopathy: 2 cases and a literature review of the expanding clinico-radiological phenotype. Eur J Paediatr Neurol 19:106–113.  https://doi.org/10.1016/j.ejpn.2014.11.010 CrossRefPubMedGoogle Scholar
  117. Sondhi V, Chakrabarty B, Kumar A et al (2016) RANBP2 mutation in an Indian child with recurrent acute necrotizing encephalopathy. Brain Dev 38:937–942.  https://doi.org/10.1016/j.braindev.2016.05.007 CrossRefPubMedGoogle Scholar
  118. Stoffler D, Feja B, Fahrenkrog B et al (2003) Cryo-electron tomography provides novel insights into nuclear pore architecture: implications for nucleocytoplasmic transport. J Mol Biol 328:119–130CrossRefGoogle Scholar
  119. Suntharalingam M, Wente SR (2003) Peering through the pore: nuclear pore complex structure, assembly, and function. Dev Cell 4:775–789CrossRefGoogle Scholar
  120. Suri M (2010) Genetic basis for acute necrotizing encephalopathy of childhood. Dev Med Child Neurol 52:4–5.  https://doi.org/10.1111/j.1469-8749.2009.03495.x CrossRefPubMedGoogle Scholar
  121. Tarazón E, Rivera M, Roselló-Lletí E et al (2012) Heart failure induces significant changes in nuclear pore complex of human cardiomyocytes. PLOS One 7:e48957.  https://doi.org/10.1371/journal.pone.0048957 CrossRefPubMedPubMedCentralGoogle Scholar
  122. The Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983CrossRefGoogle Scholar
  123. Tsai J (2011) Establishing vertebrate model systems for the study of Gle1 mediated motor neuron disease. UC, San DiegoGoogle Scholar
  124. Tullio-Pelet A, Salomon R, Hadj-Rabia S et al (2000) Mutant WD-repeat protein in triple-A syndrome. Nat Genet 26:332–335.  https://doi.org/10.1038/81642 CrossRefPubMedGoogle Scholar
  125. Vuopala K, Ignatius J, Herva R (1995) Lethal arthrogryposis with anterior horn cell disease. Hum Pathol 26:12–19CrossRefGoogle Scholar
  126. Walker FO (2007) Huntington’s disease. Lancet Lond Engl 369:218–228.  https://doi.org/10.1016/S0140-6736(07)60111-1 CrossRefGoogle Scholar
  127. Wang GF, Li W, Li K (2010) Acute encephalopathy and encephalitis caused by influenza virus infection. Curr Opin Neurol 23:305–311CrossRefGoogle Scholar
  128. Watkins JL, Murphy R, Emtage JL, Wente SR (1998) The human homologue of Saccharomyces cerevisiae Gle1p is required for poly(A) + RNA export. Proc Natl Acad Sci USA 95:6779–6784CrossRefGoogle Scholar
  129. Weinberg-Shukron A, Renbaum P, Kalifa R et al (2015) A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis. J Clin Invest 125:4295–4304.  https://doi.org/10.1172/JCI83553 CrossRefPubMedPubMedCentralGoogle Scholar
  130. Werner A, Flotho A, Melchior F (2012) The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase. Mol Cell 46:287–298.  https://doi.org/10.1016/j.molcel.2012.02.017 CrossRefPubMedGoogle Scholar
  131. Wilkie GS, Korfali N, Swanson SK et al (2011) Several novel nuclear envelope transmembrane proteins identified in skeletal muscle have cytoskeletal associations. Mol Cell Proteomics MCP.  https://doi.org/10.1074/mcp.M110.003129 CrossRefPubMedGoogle Scholar
  132. Wolf K, Schmitt-Mechelke T, Kollias S, Curt A (2013) Acute necrotizing encephalopathy (ANE1): rare autosomal-dominant disorder presenting as acute transverse myelitis. J Neurol 260:1545–1553.  https://doi.org/10.1007/s00415-012-6825-7 CrossRefPubMedGoogle Scholar
  133. Wu X, Wu W, Pan W et al (2015) Acute necrotizing encephalopathy: an underrecognized clinicoradiologic disorder. Mediators Inflamm 2015:792578.  https://doi.org/10.1155/2015/792578 CrossRefPubMedPubMedCentralGoogle Scholar
  134. Yaseen NR, Blobel G (1997) Cloning and characterization of human karyopherin beta3. Proc Natl Acad Sci USA 94:4451–4456CrossRefGoogle Scholar
  135. Zarei S, Carr K, Reiley L et al (2015) A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int 6:171.  https://doi.org/10.4103/2152-7806.169561 CrossRefPubMedPubMedCentralGoogle Scholar
  136. Zhang X, Chen S, Yoo S et al (2008) Mutation in nuclear pore component NUP155 leads to atrial fibrillation and early sudden cardiac death. Cell 135:1017–1027.  https://doi.org/10.1016/j.cell.2008.10.022 CrossRefPubMedGoogle Scholar
  137. Zhang K, Donnelly CJ, Haeusler AR et al (2015) The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525:56–61.  https://doi.org/10.1038/nature14973 CrossRefPubMedPubMedCentralGoogle Scholar
  138. Zhang K, Daigle JG, Cunningham KM et al (2018) Stress granule assembly disrupts nucleocytoplasmic transport. Cell 173:958–971.e17.  https://doi.org/10.1016/j.cell.2018.03.025 CrossRefPubMedGoogle Scholar
  139. Zuccolo M, Alves A, Galy V et al (2007) The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions. EMBO J 26:1853–1864.  https://doi.org/10.1038/sj.emboj.7601642 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Molecular Biology and MedicineUniversité Libre de BruxellesGosseliesBelgium

Personalised recommendations