Caenorhabditis elegans Nuclear Pore Complexes in Genome Organization and Gene Expression



The nuclear pore complex (NPC) serves as gateway for transport between the cytoplasm and the nucleus and its structure as well as individual components (nucleoporins or nups) are conserved among all eukaryotes, suggesting they evolved in an ancient common ancestor. In addition to their role in nucleocytoplasmic transport, nups located either at NPCs or in the nucleoplasm participate in regulation of gene expression, DNA repair and chromosome segregation during cell division. Far from being a static structure, recent studies have demonstrated that alterations in NPC composition or function occur as consequences of normal cell differentiation, physiological aging and disease. In this review, we discuss how the popular model organism Caenorhabditis elegans has contributed to our understanding of NPC biogenesis and function from single cell resolution in young embryos to organismal homeostasis in adults.


Caenorhabditis elegans development gene expression NPC npp nuclear organization nuclear pore complex nucleocytoplasmic transport nucleoporin 



Our laboratory is supported by the Spanish Ministry of Economy and Competitiveness (BFU2013-42709-P, BFU2016-79313-P and BES-2014-068609), the European COST Program (BM1408 GENiE) and the European Regional Development Fund. We are grateful to Thomas Schwartz for help with prediction of “missing” C. elegans nups and to Agnieszka Dobrzynska for critical reading of the manuscript.


  1. Alber F, Dokudovskaya S, Veenhoff LM et al (2007) Determining the architectures of macromolecular assemblies. Nature 450(7170):683–694. CrossRefPubMedGoogle Scholar
  2. Askjaer P, Ercan S, Meister P (2014a) Modern techniques for the analysis of chromatin and nuclear organization in C. elegans. WormBook:1–35.
  3. Askjaer P, Galy V, Hannak E et al (2002) Ran GTPase cycle and importins alpha and beta are essential for spindle formation and nuclear envelope assembly in living Caenorhabditis elegans embryos. Mol Biol Cell 13(12):4355–4370CrossRefPubMedPubMedCentralGoogle Scholar
  4. Askjaer P, Galy V, Meister P (2014b) Modern tools to study nuclear pore complexes and nucleocytoplasmic transport in Caenorhabditis elegans. Methods Cell Biol 122:277–310. CrossRefPubMedGoogle Scholar
  5. Audhya A, Desai A, Oegema K (2007) A role for Rab5 in structuring the endoplasmic reticulum. J Cell Biol 178(1):43–56CrossRefPubMedPubMedCentralGoogle Scholar
  6. Barton LJ, Soshnev AA, Geyer PK (2015) Networking in the nucleus: a spotlight on LEM-domain proteins. Curr Opin Cell Biol 34:1–8. CrossRefPubMedPubMedCentralGoogle Scholar
  7. Boxem M, Srinivasan DG, van den Heuvel S (1999) The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase required for M phase in meiotic and mitotic cell divisions, but not for S phase. Development 126(10):2227–2239PubMedGoogle Scholar
  8. Brachner A, Foisner R (2011) Evolvement of LEM proteins as chromatin tethers at the nuclear periphery. Biochem Soc Trans 39(6):1735–1741. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Burns LT, Wente SR (2014) From hypothesis to mechanism: uncovering nuclear pore complex links to gene expression. Mol Cell Biol 34(12):2114–2120. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Cabianca DS, Gasser SM (2016) Spatial segregation of heterochromatin: uncovering functionality in a multicellular organism. Nucleus 7(3):301–307. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Casadio A, Longman D, Hug N et al (2015) Identification and characterization of novel factors that act in the nonsense-mediated mRNA decay pathway in nematodes, flies and mammals. EMBO Rep 16(1):71–78. CrossRefPubMedGoogle Scholar
  12. Chadrin A, Hess B, San Roman M et al (2010) Pom33, a novel transmembrane nucleoporin required for proper nuclear pore complex distribution. J Cell Biol 189(5):795–811. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Chase D, Serafinas C, Ashcroft N et al (2000) The polo-like kinase PLK-1 is required for nuclear envelope breakdown and the completion of meiosis in Caenorhabditis elegans. Genesis 26(1):26–41CrossRefPubMedGoogle Scholar
  14. Chen X, Wang Y, Chen YZ et al (2016) Regulation of CED-3 caspase localization and activation by C. elegans nuclear-membrane protein NPP-14. Nat Struct Mol Biol 23(11):958–964. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Cohen M, Feinstein N, Wilson KL et al (2003) Nuclear pore protein gp210 is essential for viability in HeLa cells and Caenorhabditis elegans. Mol Biol Cell 14(10):4230–4237. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Cohen-Fix O, Askjaer P (2017) Cell Biology of the Caenorhabditis elegans Nucleus. Genetics 205(1):25–59. CrossRefPubMedGoogle Scholar
  17. D’Angelo MA, Gomez-Cavazos JS, Mei A et al (2012) A change in nuclear pore complex composition regulates cell differentiation. Dev Cell 22(2):446–458. CrossRefPubMedPubMedCentralGoogle Scholar
  18. D’Angelo MA, Raices M, Panowski SH et al (2009) Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells. Cell 136(2):284–295. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Devos D, Dokudovskaya S, Williams R et al (2006) Simple fold composition and modular architecture of the nuclear pore complex. Proc Natl Acad Sci U S A 103(7):2172–2177CrossRefPubMedPubMedCentralGoogle Scholar
  20. Dobrzynska A, Askjaer P, Gruenbaum Y (2016a) Lamin-binding proteins in Caenorhabditis elegans. Methods Enzymol 569:455–483. CrossRefPubMedGoogle Scholar
  21. Dobrzynska A, Gonzalo S, Shanahan C et al (2016b) The nuclear lamina in health and disease. Nucleus 7(3):233–248. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Fakhouri TH, Stevenson J, Chisholm AD et al (2010) Dynamic chromatin organization during foregut development mediated by the organ selector gene PHA-4/FoxA. PLoS Genet 6 (8).
  23. Fernandez AG, Piano F (2006) MEL-28 is downstream of the Ran cycle and is required for nuclear-envelope function and chromatin maintenance. Curr Biol 16(17):1757–1763CrossRefPubMedGoogle Scholar
  24. Ferreira J, Stear JH, Saumweber H (2017) Nucleoporins NPP-10, NPP-13 and NPP-20 are required for HCP-4 nuclear import to establish correct centromere assembly. J Cell Sci 130(5):963–974. CrossRefPubMedGoogle Scholar
  25. Franz C, Askjaer P, Antonin W et al (2005) Nup155 regulates nuclear envelope and nuclear pore complex formation in nematodes and vertebrates. EMBO J 24(20):3519–3531CrossRefPubMedPubMedCentralGoogle Scholar
  26. Galy V, Antonin W, Jaedicke A et al (2008) A role for gp210 in mitotic nuclear-envelope breakdown. J Cell Sci 121(Pt 3):317–328. CrossRefPubMedGoogle Scholar
  27. Galy V, Askjaer P, Franz C et al (2006) MEL-28, a novel nuclear-envelope and kinetochore protein essential for zygotic nuclear-envelope assembly in C. elegans. Curr Biol 16(17):1748–1756CrossRefPubMedGoogle Scholar
  28. Galy V, Mattaj IW, Askjaer P (2003) Caenorhabditis elegans nucleoporins Nup93 and Nup205 determine the limit of nuclear pore complex size exclusion in vivo. Mol Biol Cell 14(12):5104–5115CrossRefPubMedPubMedCentralGoogle Scholar
  29. Gerstein MB, Lu ZJ, Van Nostrand EL et al (2010) Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 330(6012):1775–1787. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Golden A, Liu J, Cohen-Fix O (2009) Inactivation of the C. elegans lipin homolog leads to ER disorganization and to defects in the breakdown and reassembly of the nuclear envelope. J Cell Sci 122(Pt 12):1970–1978. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Gomez-Cavazos JS, Hetzer MW (2012) Outfits for different occasions: tissue-specific roles of Nuclear Envelope proteins. Curr Opin Cell Biol 24(6):775–783. CrossRefPubMedPubMedCentralGoogle Scholar
  32. Gomez-Saldivar G, Fernandez A, Hirano Y et al (2016) Identification of conserved MEL-28/ELYS domains with essential roles in nuclear assembly and chromosome segregation. PLoS Genet 12(6):e1006131. CrossRefPubMedPubMedCentralGoogle Scholar
  33. Gonzalez-Aguilera C, Askjaer P (2012) Dissecting the NUP107 complex: multiple components and even more functions. Nucleus 3(4):340–348. CrossRefPubMedGoogle Scholar
  34. Gonzalez-Aguilera C, Ikegami K, Ayuso C et al (2014a) Genome-wide analysis links emerin to neuromuscular junction activity in Caenorhabditis elegans. Genome Biol 15(2):R21. CrossRefPubMedPubMedCentralGoogle Scholar
  35. Gonzalez-Aguilera C, Palladino F, Askjaer P (2014b) C. elegans epigenetic regulation in development and aging. Brief Funct Genomics 13(3):223–234. CrossRefPubMedGoogle Scholar
  36. Gonzalez-Sandoval A, Towbin BD, Kalck V et al (2015) Perinuclear anchoring of H3K9-methylated chromatin stabilizes induced cell fate in C. elegans embryos. Cell 163(6):1333–1347. CrossRefPubMedGoogle Scholar
  37. Gonzalo S, Kreienkamp R, Askjaer P (2017) Hutchinson-Gilford Progeria Syndrome: a premature aging disease caused by LMNA gene mutations. Ageing Res Rev 33:18–29. CrossRefPubMedGoogle Scholar
  38. Gorjanacz M, Klerkx EP, Galy V et al (2007) Caenorhabditis elegans BAF-1 and its kinase VRK-1 participate directly in post-mitotic nuclear envelope assembly. EMBO J 26(1):132–143CrossRefPubMedGoogle Scholar
  39. Gorjanacz M, Mattaj IW (2009) Lipin is required for efficient breakdown of the nuclear envelope in Caenorhabditis elegans. J Cell Sci 122(Pt 12):1963–1969. CrossRefPubMedGoogle Scholar
  40. Grill B, Chen L, Tulgren ED et al (2012) RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans. J Neurosci 32(8):2628–2636. CrossRefPubMedPubMedCentralGoogle Scholar
  41. Hachet V, Busso C, Toya M et al (2012) The nucleoporin Nup205/NPP-3 is lost near centrosomes at mitotic onset and can modulate the timing of this process in Caenorhabditis elegans embryos. Mol Biol Cell 23(16):3111–3121. CrossRefPubMedPubMedCentralGoogle Scholar
  42. Hachet V, Canard C, Gonczy P (2007) Centrosomes promote timely mitotic entry in C. elegans embryos. Dev Cell 12(4):531–541. CrossRefPubMedGoogle Scholar
  43. Haithcock E, Dayani Y, Neufeld E et al (2005) Age-related changes of nuclear architecture in Caenorhabditis elegans. Proc Natl Acad Sci U S A 102(46):16690–16695CrossRefPubMedPubMedCentralGoogle Scholar
  44. Hajeri VA, Little BA, Ladage ML et al (2010) NPP-16/Nup50 function and CDK-1 inactivation are associated with anoxia-induced prophase arrest in Caenorhabditis elegans. Mol Biol Cell 21(5):712–724. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Harel A, Orjalo AV, Vincent T et al (2003) Removal of a single pore subcomplex results in vertebrate nuclei devoid of nuclear pores. Mol Cell 11(4):853–864CrossRefPubMedGoogle Scholar
  46. Harr JC, Gonzalez-Sandoval A, Gasser SM (2016) Histones and histone modifications in perinuclear chromatin anchoring: from yeast to man. EMBO Rep 17(2):139–155. CrossRefPubMedPubMedCentralGoogle Scholar
  47. Hattersley N, Cheerambathur D, Moyle M et al (2016) A nucleoporin docks protein phosphatase 1 to direct meiotic chromosome segregation and nuclear assembly. Dev Cell 38(5):463–477. CrossRefPubMedPubMedCentralGoogle Scholar
  48. Hoelz A, Debler EW, Blobel G (2011) The structure of the nuclear pore complex. Annu Rev Biochem 80:613–643. CrossRefPubMedGoogle Scholar
  49. Ibarra A, Hetzer MW (2015) Nuclear pore proteins and the control of genome functions. Genes Dev 29(4):337–349. CrossRefPubMedPubMedCentralGoogle Scholar
  50. Ikegami K, Egelhofer TA, Strome S et al (2010) Caenorhabditis elegans chromosome arms are anchored to the nuclear membrane via discontinuous association with LEM-2. Genome Biol 11(12):R120. CrossRefPubMedPubMedCentralGoogle Scholar
  51. Ikegami K, Lieb JD (2013) Integral nuclear pore proteins bind to Pol III-transcribed genes and are required for Pol III transcript processing in C. elegans. Mol Cell 51(6):840–849. CrossRefPubMedPubMedCentralGoogle Scholar
  52. Joseph-Strauss D, Gorjanacz M, Santarella-Mellwig R et al (2012) Sm protein down-regulation leads to defects in nuclear pore complex disassembly and distribution in C. elegans embryos. Dev Biol 365(2):445–457. CrossRefPubMedPubMedCentralGoogle Scholar
  53. Kim JK, Gabel HW, Kamath RS et al (2005) Functional genomic analysis of RNA interference in C. elegans. Science 308(5725):1164–1167. CrossRefPubMedGoogle Scholar
  54. Knockenhauer KE, Schwartz TU (2016) The nuclear pore complex as a flexible and dynamic gate. Cell 164(6):1162–1171. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Lupu F, Alves A, Anderson K et al (2008) Nuclear pore composition regulates neural stem/progenitor cell differentiation in the mouse embryo. Dev Cell 14(6):831–842. CrossRefPubMedPubMedCentralGoogle Scholar
  56. Mansfeld J, Guttinger S, Hawryluk-Gara LA et al (2006) The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex assembly in vertebrate cells. Mol Cell 22(1):93–103CrossRefPubMedGoogle Scholar
  57. Martino L, Morchoisne-Bolhy S, Cheerambathur DK et al (2017) Channel Nucleoporins Recruit PLK-1 to Nuclear Pore Complexes to Direct Nuclear Envelope Breakdown in C. elegans. Dev Cell 43(2):157–171.e7. CrossRefPubMedGoogle Scholar
  58. Mattout A, Pike BL, Towbin BD et al (2011) An EDMD mutation in C. elegans lamin blocks muscle-specific gene relocation and compromises muscle integrity. Curr Biol 21(19):1603–1614. CrossRefPubMedGoogle Scholar
  59. Meister P, Towbin BD, Pike BL et al (2010) The spatial dynamics of tissue-specific promoters during C. elegans development. Genes Dev 24(8):766–782. CrossRefPubMedPubMedCentralGoogle Scholar
  60. Morales-Martinez A, Dobrzynska A, Askjaer P (2015) Inner nuclear membrane protein LEM-2 is required for correct nuclear separation and morphology in C. elegans. J Cell Sci 128(6):1090–1096. CrossRefPubMedGoogle Scholar
  61. Noatynska A, Panbianco C, Gotta M (2010) SPAT-1/Bora acts with Polo-like kinase 1 to regulate PAR polarity and cell cycle progression. Development 137(19):3315–3325. CrossRefPubMedGoogle Scholar
  62. O’Rourke SM, Dorfman MD, Carter JC et al (2007) Dynein modifiers in C. elegans: light chains suppress conditional heavy chain mutants. PLoS Genet 3(8):e128. CrossRefPubMedPubMedCentralGoogle Scholar
  63. Olsson M, Scheele S, Ekblom P (2004) Limited expression of nuclear pore membrane glycoprotein 210 in cell lines and tissues suggests cell-type specific nuclear pores in metazoans. Exp Cell Res 292(2):359–370CrossRefPubMedGoogle Scholar
  64. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  65. Perez-Jimenez MM, Rodriguez-Palero MJ, Rodenas E et al (2014) Age-dependent changes of nuclear morphology are uncoupled from longevity in Caenorhabditis elegans IGF/insulin receptor daf-2 mutants. Biogerontology 15(3):279–288. CrossRefPubMedGoogle Scholar
  66. Pinkston-Gosse J, Kenyon C (2007) DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans. Nat Genet 39(11):1403–1409. CrossRefPubMedGoogle Scholar
  67. Portier N, Audhya A, Maddox PS et al (2007) A microtubule-independent role for centrosomes and aurora a in nuclear envelope breakdown. Dev Cell 12(4):515–529CrossRefPubMedPubMedCentralGoogle Scholar
  68. Putker M, Madl T, Vos HR et al (2013) Redox-dependent control of FOXO/DAF-16 by transportin-1. Mol Cell 49(4):730–742. CrossRefPubMedGoogle Scholar
  69. Rahman MM, Munzig M, Kaneshiro K et al (2015) Caenorhabditis elegans polo-like kinase PLK-1 is required for merging parental genomes into a single nucleus. Mol Biol Cell 26(25):4718–4735. CrossRefPubMedPubMedCentralGoogle Scholar
  70. Raices M, D’Angelo MA (2012) Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions. Nat Rev Mol Cell Biol 13(11):687–699. CrossRefPubMedGoogle Scholar
  71. Rodenas E, Gonzalez-Aguilera C, Ayuso C et al (2012) Dissection of the NUP107 nuclear pore subcomplex reveals a novel interaction with spindle assembly checkpoint protein MAD1 in Caenorhabditis elegans. Mol Biol Cell 23(5):930–944. CrossRefPubMedPubMedCentralGoogle Scholar
  72. Rodenas E, Klerkx EP, Ayuso C et al (2009) Early embryonic requirement for nucleoporin Nup35/NPP-19 in nuclear assembly. Dev Biol 327(2):399–409. CrossRefPubMedGoogle Scholar
  73. Rohner S, Kalck V, Wang X et al (2013) Promoter- and RNA polymerase II-dependent hsp-16 gene association with nuclear pores in Caenorhabditis elegans. J Cell Biol 200(5):589–604. CrossRefPubMedPubMedCentralGoogle Scholar
  74. Roy SH, Clayton JE, Holmen J et al (2011) Control of Cdc14 activity coordinates cell cycle and development in Caenorhabditis elegans. Mech Dev 128(7-10):317–326. CrossRefPubMedPubMedCentralGoogle Scholar
  75. Schetter A, Askjaer P, Piano F et al (2006) Nucleoporins NPP-1, NPP-3, NPP-4, NPP-11 and NPP-13 are required for proper spindle orientation in C. elegans. Dev Biol 289(2):360–371CrossRefPubMedGoogle Scholar
  76. Sharma R, Jost D, Kind J et al (2014) Differential spatial and structural organization of the X chromosome underlies dosage compensation in C. elegans. Genes Dev 28(23):2591–2596. CrossRefPubMedPubMedCentralGoogle Scholar
  77. Sheth U, Pitt J, Dennis S et al (2010) Perinuclear P granules are the principal sites of mRNA export in adult C. elegans germ cells. Development 137(8):1305–1314. CrossRefPubMedPubMedCentralGoogle Scholar
  78. Solovei I, Thanisch K, Feodorova Y (2016) How to rule the nucleus: divide et impera. Curr Opin Cell Biol 40:47–59. CrossRefPubMedGoogle Scholar
  79. Sonneville R, Craig G, Labib K et al (2015) Both chromosome decondensation and condensation are dependent on DNA replication in C. elegans embryos. Cell Reports 12(3):405–417. CrossRefPubMedPubMedCentralGoogle Scholar
  80. Stavru F, Hulsmann BB, Spang A et al (2006) NDC1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes. J Cell Biol 173(4):509–519. CrossRefPubMedPubMedCentralGoogle Scholar
  81. Stuwe T, Correia AR, Lin DH et al (2015) Nuclear pores. Architecture of the nuclear pore complex coat. Science 347(6226):1148–1152. CrossRefPubMedPubMedCentralGoogle Scholar
  82. Tavernier N, Noatynska A, Panbianco C et al (2015) Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos. J Cell Biol 208(6):661–669. CrossRefPubMedPubMedCentralGoogle Scholar
  83. Tintori SC, Osborne Nishimura E, Golden P et al (2016) A Transcriptional lineage of the early C. elegans embryo. Dev Cell 38(4):430–444. CrossRefPubMedPubMedCentralGoogle Scholar
  84. Towbin BD, Gonzalez-Aguilera C, Sack R et al (2012) Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell 150(5):934–947. CrossRefPubMedGoogle Scholar
  85. Updike DL, Hachey SJ, Kreher J et al (2011) P granules extend the nuclear pore complex environment in the C. elegans germ line. J Cell Biol 192(6):939–948. CrossRefPubMedPubMedCentralGoogle Scholar
  86. Updike DL, Strome S (2009) A genomewide RNAi screen for genes that affect the stability, distribution and function of P granules in Caenorhabditis elegans. Genetics 183(4):1397–1419. CrossRefPubMedPubMedCentralGoogle Scholar
  87. van Haaften G, Romeijn R, Pothof J et al (2006) Identification of conserved pathways of DNA-damage response and radiation protection by genome-wide RNAi. Curr Biol 16(13):1344–1350. CrossRefPubMedGoogle Scholar
  88. Vastenhouw NL, Fischer SE, Robert VJ et al (2003) A genome-wide screen identifies 27 genes involved in transposon silencing in C. elegans. Curr Biol 13(15):1311–1316CrossRefPubMedGoogle Scholar
  89. Vollmer B, Antonin W (2014) The diverse roles of the Nup93/Nic96 complex proteins – structural scaffolds of the nuclear pore complex with additional cellular functions. Biol Chem 395(5):515–528. CrossRefPubMedGoogle Scholar
  90. Voronina E, Seydoux G (2010) The C. elegans homolog of nucleoporin Nup98 is required for the integrity and function of germline P granules. Development 137(9):1441–1450. CrossRefPubMedPubMedCentralGoogle Scholar
  91. Walther TC, Alves A, Pickersgill H et al (2003) The conserved Nup107-160 complex is critical for nuclear pore complex assembly. Cell 113(2):195–206CrossRefPubMedGoogle Scholar
  92. Winter JF, Hopfner S, Korn K et al (2012) Caenorhabditis elegans screen reveals role of PAR-5 in RAB-11-recycling endosome positioning and apicobasal cell polarity. Nat Cell Biol 14(7):666–676. CrossRefPubMedGoogle Scholar
  93. Wu L, Zhou B, Oshiro-Rapley N et al (2016) An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer. Cell 167(7):1705–1718.e13. CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Andalusian Center for Developmental BiologyCSIC/Junta de Andalucia/Universidad Pablo de OlavideSevilleSpain

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