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Molecular basis for the functional interaction of dynein light chain with the nuclear-pore complex


Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope1. Here, we discovered an unexpected role for yeast dynein light chain (Dyn2)2 in the NPC. Dyn2 is a previously undescribed nucleoporin that functions as molecular glue to dimerize and stabilize the Nup82–Nsp1–Nup159 complex, a module of the cytoplasmic pore filaments3. Biochemical analyses showed that Dyn2 binds to a linear motif (termed DIDNup159) inserted between the Phe-Gly repeat and coiled-coil domain of Nup159. Electron microscopy revealed that the reconstituted Dyn2–DIDNup159 complex forms a rigid rod-like structure, in which five Dyn2 homodimers align like 'pearls on a string' between two extented DIDNup159 strands. These findings imply that the rigid 20 nm long Dyn2–DIDNup159 filament projects the Nup159 Phe-Gly repeats from the Nup82 module. Thus, it is possible that dynein light chain plays a role in organizing natively unfolded Phe-Gly repeats within the NPC scaffold to facilitate nucleocytoplasmic transport.

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Figure 1: Yeast dynein light chain (Dyn2) is associated with the Nup82 complex.
Figure 2: A dynein light chain interacting domain (DID) in Nup159.
Figure 3: Dyn2 regulates dimerization of the Nup82 complex.
Figure 4: Functional interaction between Dyn2 and the Nup82 complex.
Figure 5: Electron microscopy analysis of the interaction between Dyn2 and DIDNup159.

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Protein Data Bank


  1. 1

    Hetzer, M. W., Walther, T. C. & Mattaj, I. W. Pushing the envelope: structure, function, and dynamics of the nuclear periphery. Annu. Rev. Cell. Dev. Biol. 21, 347–380 (2005).

    CAS  Article  Google Scholar 

  2. 2

    Dick, T., Surana, U. & Chia, W. Molecular and genetic characterization of SLC1, a putative Saccharomyces cerevisiae homolog of the metazoan cytoplasmic dynein light chain 1. Mol. Gen. Genet. 251, 38–43 (1996).

    CAS  PubMed  Google Scholar 

  3. 3

    Cole, C. N. & Scarcelli, J. J. Transport of messenger RNA from the nucleus to the cytoplasm. Curr. Opin. Cell Biol. 18, 299–306 (2006).

    CAS  Article  Google Scholar 

  4. 4

    Schwartz, T. U. Modularity within the architecture of the nuclear pore complex. Curr. Opin. Struct. Biol. 15, 221–226 (2005).

    CAS  Article  Google Scholar 

  5. 5

    Beck, M. et al. Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science 306, 1387–1390 (2004).

    CAS  Article  Google Scholar 

  6. 6

    Rout, M. P. et al. The yeast nuclear pore complex: composition, architecture, and transport mechanism. J. Cell Biol. 148, 635–651 (2000).

    CAS  Article  Google Scholar 

  7. 7

    Hurwitz, M. E., Strambio-de-Castillia, C. & Blobel, G. Two yeast nuclear pore complex proteins involved in mRNA export form a cytoplasmically oriented subcomplex. Proc. Natl Acad. Sci. USA 95, 11241–11245 (1998).

    CAS  Article  Google Scholar 

  8. 8

    Belgareh, N. et al. Functional characterization of a Nup159p-containing nuclear pore subcomplex. Mol. Biol. Cell. 9, 3475–3492 (1998).

    CAS  Article  Google Scholar 

  9. 9

    Weirich, C. S., Erzberger, J. P., Berger, J. M. & Weis, K. The N-terminal domain of Nup159 forms a β-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore. Mol. Cell 16, 749–760 (2004).

    CAS  Article  Google Scholar 

  10. 10

    Denning, D. P., Patel, S. S., Uversky, V., Fink, A. L. & Rexach, M. Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded. Proc. Natl Acad. Sci. USA 100, 2450–2455 (2003).

    CAS  Article  Google Scholar 

  11. 11

    Vallee, R. B., Williams, J. C., Varma, D. & Barnhart, L. E. Dynein: An ancient motor protein involved in multiple modes of transport. J. Neurobiol. 58, 189–200 (2004).

    CAS  Article  Google Scholar 

  12. 12

    Fan, J. S. et al. Protein inhibitor of neuronal nitric-oxide synthase, PIN, binds to a 17-amino acid residue fragment of the enzyme. J. Biol. Chem. 273, 33472–33481 (1998).

    CAS  Article  Google Scholar 

  13. 13

    Navarro-Lerida, I. et al. Proteomic identification of brain proteins that interact with dynein light chain LC8. Proteomics 4, 339–346 (2004).

    CAS  Article  Google Scholar 

  14. 14

    Liang, J., Jaffrey, S. R., Guo, W., Snyder, S. H. & Clardy, J. Structure of the PIN/LC8 dimer with a bound peptide. Nature Struct. Biol. 6, 735–740 (1999).

    CAS  Article  Google Scholar 

  15. 15

    Fan, J., Zhang, Q., Tochio, H., Li, M. & Zhang, M. Structural basis of diverse sequence-dependent target recognition by the 8 kDa dynein light chain. J. Mol. Biol. 306, 97–108 (2001).

    CAS  Article  Google Scholar 

  16. 16

    Hodge, C. A., Colot, H. V., Stafford, P. & Cole, C. N. Rat8p/Dbp5p is a shuttling transport factor that interacts with Rat7p/Nup159p and Gle1p and suppresses the mRNA export defect of xpo1-1 cells. EMBO J. 18, 5778–5788 (1999).

    CAS  Article  Google Scholar 

  17. 17

    Komori, M. et al. The Hansenula polymorpha PEX14 gene encodes a novel peroxisomal membrane protein essential for peroxisome biogenesis. EMBO J. 16, 44–53 (1997).

    CAS  Article  Google Scholar 

  18. 18

    Doye, V., Wepf, R. & Hurt, E. C. A novel nuclear pore protein Nup133p with distinct roles in poly (A)+ RNA transport and nuclear pore distribution. EMBO J. 13, 6062–6075 (1994).

    CAS  Article  Google Scholar 

  19. 19

    Sheeman, B. et al. Determinants of S. cerevisiae dynein localization and activation: implications for the mechanism of spindle positioning. Curr. Biol. 13, 364–372 (2003).

    CAS  Article  Google Scholar 

  20. 20

    Nyarko, A. et al. Ionization of His 55 at the dimer interface of dynein light-chain LC8 is coupled to dimer dissociation. Biochemistry 44, 14248–14255 (2005).

    CAS  Article  Google Scholar 

  21. 21

    Bailer, S. M., Balduf, C. & Hurt, E. C. The Nsp1p carboxy-terminal domain is organized in functionally distinct coiled-coil regions required for assembly of nucleoporin subcomplexes and nucleocytoplasmic transport. Mol. Cell Biol. 21, 7944–7955 (2001).

    CAS  Article  Google Scholar 

  22. 22

    Grandi, P. et al. A novel nuclear pore protein Nup82p which specifically binds to a fraction of Nsp1p. J. Cell Biol. 130, 1263–1273 (1995).

    CAS  Article  Google Scholar 

  23. 23

    Gorsch, L. C., Dockendorff, T. C. & Cole, C. N. A conditional allele of the novel repeat-containing yeast nucleoporin RAT7/NUP159 causes both rapid cessation of mRNA export and reversible clustering of nuclear pore complexes. J. Cell Biol. 129, 939–955 (1995).

    CAS  Article  Google Scholar 

  24. 24

    Miki, F. et al. The 14-kDa dynein light chain-family protein Dlc1 is required for regular oscillatory nuclear movement and efficient recombination during meiotic prophase in fission yeast. Mol. Biol. Cell. 13, 930–946 (2002).

    CAS  Article  Google Scholar 

  25. 25

    Stewart, M. Molecular mechanism of the nuclear protein import cycle. Nature Rev. Mol. Cell. Biol. 8, 195–208 (2007).

    CAS  Article  Google Scholar 

  26. 26

    Bernad, R., van der Velde, H., Fornerod, M. & Pickersgill, H. Nup358/RanBP2 attaches to the nuclear pore complex via association with Nup88 and Nup214/CAN and plays a supporting role in CRM1-mediated nuclear protein export. Mol. Cell Biol. 24, 2373–2384 (2004).

    CAS  Article  Google Scholar 

  27. 27

    Walther, T. C. et al. The cytoplasmic filaments of the nuclear pore complex are dispensable for selective nuclear protein import. J. Cell Biol. 158, 63–77 (2002).

    CAS  Article  Google Scholar 

  28. 28

    Delphin, C., Guan, T., Melchior, F. & Gerace, L. RanGTP targets p97 to RanBP2, a filamentous protein localized at the cytoplasmic periphery of the nuclear pore complex. Mol. Biol. Cell 8, 2379–2390 (1997).

    CAS  Article  Google Scholar 

  29. 29

    Puig, O. et al. New constructs and strategies for efficient PCR-based gene manipulations in yeast. Yeast 14, 1139–1146 (1998).

    CAS  Article  Google Scholar 

  30. 30

    Baßler, J. et al. Identification of a 60S pre-ribosomal particle that is closely linked to nuclear export. Mol. Cell 8, 517–529 (2001).

    Article  Google Scholar 

  31. 31

    Lutzmann, M., Kunze, R., Buerer, A., Aebi, U. & Hurt, E. Modular self-assembly of a Y-shaped multiprotein complex from seven nucleoporins. EMBO J. 21, 387–397 (2002).

    CAS  Article  Google Scholar 

  32. 32

    Lutzmann, M. et al. Reconstitution of Nup157 and Nup145N into the Nup84 complex. J. Biol. Chem. 280, 18442–18451 (2005).

    CAS  Article  Google Scholar 

  33. 33

    Dube, P., Tavares, P., Lurz, R. & van Heel, M. The portal protein of bacteriophage SPP1: a DNA pump with 13-fold symmetry. EMBO J. 12, 1303–1309 (1993).

    CAS  Article  Google Scholar 

  34. 34

    van Heel, M., Harauz, G., Orlova, E. V., Schmidt, R. & Schatz, M. A new generation of the IMAGIC image processing system. J. Struct. Biol. 116, 17–24 (1996).

    CAS  Article  Google Scholar 

  35. 35

    Pettersen, E. F. et al. UCSF chimera —a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).

    CAS  Article  Google Scholar 

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We are grateful to S. Merker, P. Ihrig and J. Lechner for performing mass spectrometry. E.H. is recipient of grants from the Deutsche Forschungsgemeinschaft (SFB 638/B2) and Fonds der Chemischen Industrie.

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Experiments were designed and data analysed and interpreted by P.S. and E.H. Strain construction, DNA recombination work, fluorescence microscopy and biochemical analyses (affinity purification, gel filtration, in vitro assays) were performed by P.S. and R.K. D.H. and P.P. performed double-flourescence microscopy. Negative-staining electron microscopy was conducted by D.F., M.D. and B.M. The manuscript was written by P.S. and E.H. All authors discussed the results and commented on the manuscript.

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Correspondence to Ed Hurt.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary figures S1, S2, S3, S4, S5, S6 and Supplementary table S1 (PDF 1204 kb)

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Stelter, P., Kunze, R., Flemming, D. et al. Molecular basis for the functional interaction of dynein light chain with the nuclear-pore complex. Nat Cell Biol 9, 788–796 (2007).

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