Skip to main content
Protein & Cell logoLink to Protein & Cell
. 2011 Apr 27;2(4):291–302. doi: 10.1007/s13238-011-1038-x

Calcium regulation of nucleocytoplasmic transport

Ashapurna Sarma 1, Weidong Yang 1,
PMCID: PMC3387809  NIHMSID: NIHMS385913  PMID: 21528351

Abstract

Bidirectional trafficking of macromolecules between the cytoplasm and the nucleus is mediated by the nuclear pore complexes (NPCs) embedded in the nuclear envelope (NE) of eukaryotic cell. The NPC functions as the sole pathway to allow for the passive diffusion of small molecules and the facilitated translocation of larger molecules. Evidence shows that these two transport modes and the conformation of NPC can be regulated by calcium stored in the lumen of nuclear envelope and endoplasmic reticulum. However, the mechanism of calcium regulation remains poorly understood. In this review, we integrate data on the observations of calciumregulated structure and function of the NPC over the past years. Furthermore, we highlight challenges in the measurements of dynamic conformational changes and transient transport kinetics in the NPC. Finally, an innovative imaging approach, single-molecule superresolution fluorescence microscopy, is introduced and expected to provide more insights into the mechanism of calcium-regulated nucleocytoplasmic transport.

Keywords: nuclear envelope, nuclear pore complex, nucleocytoplasmic transport, calcium stores, single-molecule fluorescence microscopy

References

  1. Bayliss R., Littlewood T., Stewart M. Structural basis for the interaction between FxFG nucleoporin repeats and importinbeta in nuclear trafficking. Cell. 2000;102:99–108. doi: 10.1016/S0092-8674(00)00014-3. [DOI] [PubMed] [Google Scholar]
  2. Beck M., Förster F., Ecke M., Plitzko J.M., Melchior F., Gerisch G., Baumeister W., Medalia O. Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science. 2004;306:1387–1390. doi: 10.1126/science.1104808. [DOI] [PubMed] [Google Scholar]
  3. Bednenko J., Cingolani G., Gerace L. Importin β contains a COOH-terminal nucleoporin binding region important for nuclear transport. J Cell Biol. 2003;162:391–401. doi: 10.1083/jcb.200303085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Betzig E. Proposed method for molecular optical imaging. Opt Lett. 1995;20:237–239. doi: 10.1364/OL.20.000237. [DOI] [PubMed] [Google Scholar]
  5. Bischoff F.R., Görlich D. RanBP1 is crucial for the release of RanGTP from importin β-related nuclear transport factors. FEBS Lett. 1997;419:249–254. doi: 10.1016/S0014-5793(97)01467-1. [DOI] [PubMed] [Google Scholar]
  6. Bischoff F.R., Klebe C., Kretschmer J., Wittinghofer A., Ponstingl H. RanGAP1 induces GTPase activity of nuclear Ras-related Ran. Proc Natl Acad Sci U S A. 1994;91:2587–2591. doi: 10.1073/pnas.91.7.2587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bootman M.D., Fearnley C., Smyrnias I., MacDonald F., Roderick H.L. An update on nuclear calcium signalling. J Cell Sci. 2009;122:2337–2350. doi: 10.1242/jcs.028100. [DOI] [PubMed] [Google Scholar]
  8. Brohawn S.G., Partridge J.R., Whittle J.R.R., Schwartz T.U. Nuclear pore complex has entered the atomic age. Structure. 2009;17:1156–1168. doi: 10.1016/j.str.2009.07.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bustamante C., Bryant Z., Smith S.B. Ten years of tension: single-molecule DNA mechanics. Nature. 2003;421:423–427. doi: 10.1038/nature01405. [DOI] [PubMed] [Google Scholar]
  10. Cardarelli F., Gratton E. In vivo imaging of singlemolecule translocation through nuclear pore complexes by pair correlation functions. PLoS One. 2010;5:e10475. doi: 10.1371/journal.pone.0010475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Carmen P.T., Marisa J., David E.C. Nuclear calcium and the regulation of the nuclear pore complex. BioEssays. 1997;19:787–792. doi: 10.1002/bies.950190908. [DOI] [PubMed] [Google Scholar]
  12. Cook A., Bono F., Jinek M., Conti E. Structural biology of nucleocytoplasmic transport. Annu Rev Biochem. 2007;76:647–671. doi: 10.1146/annurev.biochem.76.052705.161529. [DOI] [PubMed] [Google Scholar]
  13. Corbett A.H., Silver P.A. Nucleocytoplasmic transport of macromolecules. Microbiol Mol Biol Rev. 1997;61:193–211. doi: 10.1128/mmbr.61.2.193-211.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Coutavas E., Ren M., Oppenheim J.D., D’Eustachio P., Rush M.G. Characterization of proteins that interact with the cellcycle regulatory protein Ran/TC4. Nature. 1993;366:585–587. doi: 10.1038/366585a0. [DOI] [PubMed] [Google Scholar]
  15. Cronshaw J.M., Krutchinsky A.N., Zhang W., Chait B.T., Matunis M.J. Proteomic analysis of the mammalian nuclear pore complex. J Cell Biol. 2002;158:915–927. doi: 10.1083/jcb.200206106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dange T., Grünwald D., Grünwald A., Peters R., Kubitscheck U. Autonomy and robustness of translocation through the nuclear pore complex: a single-molecule study. J Cell Biol. 2008;183:77–86. doi: 10.1083/jcb.200806173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Danker T., Oberleithner H. Nuclear pore function viewed with atomic force microscopy. Pflügers Arch. 2000;439:671–681. doi: 10.1007/s004240000249. [DOI] [PubMed] [Google Scholar]
  18. 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 U S A. 2003;100:2450–2455. doi: 10.1073/pnas.0437902100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Erickson E.S., Mooren O.L., Moore D., Krogmeier J.R., Dunn R. C. The role of nuclear envelope calciumin modifying nuclear pore complex structure. Can J Physiol Pharmacol. 2006;84:309–318. doi: 10.1139/y05-109. [DOI] [PubMed] [Google Scholar]
  20. Erickson E.S., Mooren O.L., Moore-Nichols D., Dunn R.C. Activation of ryanodine receptors in the nuclear envelope alters the conformation of the nuclear pore complex. Biophys Chem. 2004;112:1–7. doi: 10.1016/j.bpc.2004.06.010. [DOI] [PubMed] [Google Scholar]
  21. Fahrenkrog B., Aebi U. The nuclear pore complex: nucleocytoplasmic transport and beyond. Nat Rev Mol Cell Biol. 2003;4:757–766. doi: 10.1038/nrm1230. [DOI] [PubMed] [Google Scholar]
  22. Fernández-Suárez M., Ting A.Y. Fluorescent probes for super-resolution imaging in living cells. Nat Rev Mol Cell Biol. 2008;9:929–943. doi: 10.1038/nrm2531. [DOI] [PubMed] [Google Scholar]
  23. Frey N., McKinsey T.A., Olson E.N. Decoding calcium signals involved in cardiac growth and function. Nat Med. 2000;6:1221–1227. doi: 10.1038/81321. [DOI] [PubMed] [Google Scholar]
  24. Fried H., Kutay U. Nucleocytoplasmic transport: taking an inventory. Cell Mol Life Sci. 2003;60:1659–1688. doi: 10.1007/s00018-003-3070-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gensburger C., Freyermuth S., Klein C., Malviya A.N. In vivo nuclear Ca2+-ATPase phosphorylation triggers intermediate size molecular transport to the nucleus. Biochem Biophys Res Commun. 2003;303:1225–1228. doi: 10.1016/S0006-291X(03)00500-X. [DOI] [PubMed] [Google Scholar]
  26. Gerasimenko J., Maruyama Y., Tepikin A., Petersen O.H., Gerasimenko O. Calcium signalling in and around the nuclear envelope. Biochem Soc Trans. 2003;31:76–78. doi: 10.1042/bst0310076. [DOI] [PubMed] [Google Scholar]
  27. Greber U.F., Gerace L. Nuclear protein import is inhibited by an antibody to a lumenal epitope of a nuclear pore complex glycoprotein. J Cell Biol. 1992;116:15–30. doi: 10.1083/jcb.116.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Greber U.F., Gerace L. Depletion of calcium from the lumen of endoplasmic reticulum reversibly inhibits passive diffusion and signal-mediated transport into the nucleus. J Cell Biol. 1995;128:5–14. doi: 10.1083/jcb.128.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Greber U.F., Senior A., Gerace L. A major glycoprotein of the nuclear pore complex is a membrane-spanning polypeptide with a large lumenal domain and a small cytoplasmic tail. EMBO J. 1990;9:1495–1502. doi: 10.1002/j.1460-2075.1990.tb08267.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hess H.F., Betzig E., Harris T.D., Pfeiffer L.N., West K.W. Near-field spectroscopy of the quantum constituents of a luminescent system. Science. 1994;264:1740–1745. doi: 10.1126/science.264.5166.1740. [DOI] [PubMed] [Google Scholar]
  31. Isgro T.A., Schulten K. Binding dynamics of isolated nucleoporin repeat regions to importin-beta. Structure. 2005;13:1869–1879. doi: 10.1016/j.str.2005.09.007. [DOI] [PubMed] [Google Scholar]
  32. Izaurralde E., Kutay U., von Kobbe C., Mattaj I.W., Görlich D. The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus. EMBO J. 1997;16:6535–6547. doi: 10.1093/emboj/16.21.6535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jäggi R.D., Franco-Obregón A., Mühlhäusser P., Thomas F., Kutay U., Ensslin K. Modulation of nuclear pore topology by transport modifiers. Biophys J. 2003;84:665–670. doi: 10.1016/S0006-3495(03)74886-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kahms M., Lehrich P., Hüve J., Sanetra N., Peters R. Binding site distribution of nuclear transport receptors and transport complexes in single nuclear pore complexes. Traffic. 2009;10:1228–1242. doi: 10.1111/j.1600-0854.2009.00947.x. [DOI] [PubMed] [Google Scholar]
  35. Kass G.E., Orrenius S. Calcium signaling and cytotoxicity. Environ Health Perspect. 1999;107:25–35. doi: 10.1289/ehp.99107s125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kau T.R., Way J.C., Silver P.A. Nuclear transport and cancer: from mechanism to intervention. Nat Rev Cancer. 2004;4:106–117. doi: 10.1038/nrc1274. [DOI] [PubMed] [Google Scholar]
  37. Kramer A., Ludwig Y., Shahin V., Oberleithner H. A pathway separate from the central channel through the nuclear pore complex for inorganic ions and small macromolecules. J Biol Chem. 2007;282:31437–31443. doi: 10.1074/jbc.M703720200. [DOI] [PubMed] [Google Scholar]
  38. Kubitscheck U., Grünwald D., Hoekstra A., Rohleder D., Kues T., Siebrasse J.P., Peters R. Nuclear transport of single molecules: dwell times at the nuclear pore complex. J Cell Biol. 2005;168:233–243. doi: 10.1083/jcb.200411005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lee M.A., Dunn R.C., Clapham D.E., Stehno-Bittel L. Calcium regulation of nuclear pore permeability. Cell Calcium. 1998;23:91–101. doi: 10.1016/S0143-4160(98)90107-5. [DOI] [PubMed] [Google Scholar]
  40. Lee S.J., Matsuura Y., Liu S.M., Stewart M. Structural basis for nuclear import complex dissociation by RanGTP. Nature. 2005;435:693–696. doi: 10.1038/nature03578. [DOI] [PubMed] [Google Scholar]
  41. Lim R., Aebi U., Fahrenkrog B. Towards reconciling structure and function in the nuclear pore complex. Histoche Cell Biol. 2008;129:105–116. doi: 10.1007/s00418-007-0371-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lim R.Y.H., Fahrenkrog B., Köser J., Schwarz-Herion K., Deng J., Aebi U. Nanomechanical Basis of Selective Gating by the Nuclear Pore Complex. Science. 2007;318:640–643. doi: 10.1126/science.1145980. [DOI] [PubMed] [Google Scholar]
  43. Lippincott-Schwartz J., Patterson G.H. Photoactivatable fluorescent proteins for diffraction-limited and super-resolution imaging. Trends Cell Biol. 2009;19:555–565. doi: 10.1016/j.tcb.2009.09.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Liu S.M., Stewart M. Structural basis for the high-affinity binding of nucleoporin Nup1p to the Saccharomyces cerevisiae importin-beta homologue, Kap95p. J Mol Biol. 2005;349:515–525. doi: 10.1016/j.jmb.2005.04.003. [DOI] [PubMed] [Google Scholar]
  45. Lyman S.K., Guan T., Bednenko J., Wodrich H., Gerace L. Influence of cargo size on Ran and energy requirements for nuclear protein import. J Cell Biol. 2002;159:55–67. doi: 10.1083/jcb.200204163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Ma J., Yang W. Three-dimensional distribution of transient interactions in the nuclear pore complex obtained from single-molecule snapshots. Proc Natl Acad Sci U S A. 2010;107:7305–7310. doi: 10.1073/pnas.0908269107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Malviya A.N., Klein C. Mechanism regulating nuclear calcium signaling. Can J Physiol Pharmacol. 2006;84:403–422. doi: 10.1139/y05-130. [DOI] [PubMed] [Google Scholar]
  48. Mattson M.P., LaFerla F.M., Chan S.L., Leissring M.A., Shepel P. N., Geiger J.D. Calcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders. Trends Neurosci. 2000;23:222–229. doi: 10.1016/S0166-2236(00)01548-4. [DOI] [PubMed] [Google Scholar]
  49. Miao L., Schulten K. Transport-related structures and processes of the nuclear pore complex studied through molecular dynamics. Structure. 2009;17:449–459. doi: 10.1016/j.str.2008.12.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Moore M.S., Blobel G. The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. Nature. 1993;365:661–663. doi: 10.1038/365661a0. [DOI] [PubMed] [Google Scholar]
  51. Moore-Nichols D., Arnott A., Dunn R.C. Regulation of nuclear pore complex conformation by IP(3) receptor activation. Biophys J. 2002;83:1421–1428. doi: 10.1016/S0006-3495(02)73913-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Mooren O.L., Erickson E.S., Moore-Nichols D., Dunn R.C. Nuclear side conformational changes in the nuclear pore complex following calcium release from the nuclear membrane. Phys Biol. 2004;1:125–134. doi: 10.1088/1478-3967/1/2/008. [DOI] [PubMed] [Google Scholar]
  53. O’Brien E.M., Gomes D.A., Sehgal S., Nathanson M.H. Hormonal Regulation of Nuclear Permeability. J Biol Chem. 2007;282:4210–4217. doi: 10.1074/jbc.M606300200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Patel S.S., Belmont B.J., Sante J.M., Rexach M.F. Natively unfolded nucleoporins gate protein diffusion across the nuclear pore complex. Cell. 2007;129:83–96. doi: 10.1016/j.cell.2007.01.044. [DOI] [PubMed] [Google Scholar]
  55. Patterson G.H., Lippincott-Schwartz J. A photoactivatable GFP for selective photolabeling of proteins and cells. Science. 2002;297:1873–1877. doi: 10.1126/science.1074952. [DOI] [PubMed] [Google Scholar]
  56. Paulillo S.M., Powers M.A., Ullman K.S., Fahrenkrog B. Changes in nucleoporin domain topology in response to chemical effectors. J Mol Biol. 2006;363:39–50. doi: 10.1016/j.jmb.2006.08.021. [DOI] [PubMed] [Google Scholar]
  57. Perez-Terzic C., Gacy A.M., Bortolon R., Dzeja P.P., Puceat M., Jaconi M., Prendergast F.G., Terzic A. Structural plasticity of the cardiac nuclear pore complex in response to regulators of nuclear import. Circ Res. 1999;84:1292–1301. doi: 10.1161/01.RES.84.11.1292. [DOI] [PubMed] [Google Scholar]
  58. Perez-Terzic C., Jaconi M., Clapham D.E. Nuclear calcium and the regulation of the nuclear pore complex. BioEssays. 1997;19:787–792. doi: 10.1002/bies.950190908. [DOI] [PubMed] [Google Scholar]
  59. Perez-Terzic C., Pyle J., Jaconi M., Stehno-Bittel L., Clapham D.E. Conformational states of the nuclear pore complex induced by depletion of nuclear Ca2+ stores. Science. 1996;273:1875–1877. doi: 10.1126/science.273.5283.1875. [DOI] [PubMed] [Google Scholar]
  60. Peters R. Translocation through the nuclear pore: Kaps pave the way. Bioessays. 2009;31:466–477. doi: 10.1002/bies.200800159. [DOI] [PubMed] [Google Scholar]
  61. Rakowska A., Danker T., Schneider S.W., Oberleithner H. ATP-Induced shape change of nuclear pores visualized with the atomic force microscope. J Membr Biol. 1998;163:129–136. doi: 10.1007/s002329900377. [DOI] [PubMed] [Google Scholar]
  62. Rexach M., Blobel G. Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors, and nucleoporins. Cell. 1995;83:683–692. doi: 10.1016/0092-8674(95)90181-7. [DOI] [PubMed] [Google Scholar]
  63. Rizzuto R., Pozzan T. When calcium goes wrong: genetic alterations of a ubiquitous signaling route. Nat Genet. 2003;34:135–141. doi: 10.1038/ng0603-135. [DOI] [PubMed] [Google Scholar]
  64. Rout M.P., Aitchison J.D. The nuclear pore complex as a transport machine. J Biol Chem. 2001;276:16593–16596. doi: 10.1074/jbc.R100015200. [DOI] [PubMed] [Google Scholar]
  65. Rout M.P., Aitchison J.D., Magnasco M.O., Chait B.T. Virtual gating and nuclear transport: the hole picture. Trends Cell Biol. 2003;13:622–628. doi: 10.1016/j.tcb.2003.10.007. [DOI] [PubMed] [Google Scholar]
  66. Rout M.P., Aitchison J.D., Suprapto A., Hjertaas K., Zhao Y., Chait B.T. The yeast nuclear pore complex: composition, architecture, and transport mechanism. J Cell Biol. 2000;148:635–651. doi: 10.1083/jcb.148.4.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Rout M.P., Blobel G. Isolation of the yeast nuclear pore complex. J Cell Biol. 1993;123:771–783. doi: 10.1083/jcb.123.4.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Rout M.P., Wente S.R. Pores for thought: nuclear pore complex proteins. Trends Cell Biol. 1994;4:357–365. doi: 10.1016/0962-8924(94)90085-X. [DOI] [PubMed] [Google Scholar]
  69. Stehno-Bittel L., Lückhoff A., Clapham D.E. Calcium release from the nucleus by InsP3 receptor channels. Neuron. 1995;14:163–167. doi: 10.1016/0896-6273(95)90250-3. [DOI] [PubMed] [Google Scholar]
  70. Stehno-Bittel L., Perez-Terzic C., Clapham D.E. Diffusion across the nuclear envelope inhibited by depletion of the nuclear Ca2 + store. Science. 1995;270:1835–1838. doi: 10.1126/science.270.5243.1835. [DOI] [PubMed] [Google Scholar]
  71. Stewart M. Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol. 2007;8:195–208. doi: 10.1038/nrm2114. [DOI] [PubMed] [Google Scholar]
  72. Stoffler D., Feja B., Fahrenkrog B., Walz J., Typke D., Aebi U. Cryo-electron tomography provides novel insights into nuclear pore architecture: implications for nucleocytoplasmic transport. J Mol Biol. 2003;328:119–130. doi: 10.1016/S0022-2836(03)00266-3. [DOI] [PubMed] [Google Scholar]
  73. Stoffler D., Goldie K.N., Feja B., Aebi U. Calciummediated structural changes of native nuclear pore complexes monitored by time-lapse atomic force microscopy. J Mol Biol. 1999;287:741–752. doi: 10.1006/jmbi.1999.2637. [DOI] [PubMed] [Google Scholar]
  74. Stoffler D., Schwarz-Herion K., Aebi U., Fahrenkrog B. Getting across the nuclear pore complex: new insights into nucleocytoplasmic transport. Can J Physiol Pharmacol. 2006;84:499–507. doi: 10.1139/y06-001. [DOI] [PubMed] [Google Scholar]
  75. Strawn L.A., Shen T., Shulga N., Goldfarb D.S., Wente S.R. Minimal nuclear pore complexes define FG repeat domains essential for transport. Nat Cell Biol. 2004;6:197–206. doi: 10.1038/ncb1097. [DOI] [PubMed] [Google Scholar]
  76. Strübing C., Clapham D.E. Active nuclear import and export is independent of lumenal Ca2+ stores in intact mammalian cells. J Gen Physiol. 1999;113:239–248. doi: 10.1085/jgp.113.2.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Suntharalingam M., Wente S.R. Peering through the pore: nuclear pore complex structure, assembly, and function. Dev Cell. 2003;4:775–789. doi: 10.1016/S1534-5807(03)00162-X. [DOI] [PubMed] [Google Scholar]
  78. Thompson R.E., Larson D.R., Webb W.W. Precise nanometer localization analysis for individual fluorescent probes. Biophys J. 2002;82:2775–2783. doi: 10.1016/S0006-3495(02)75618-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Walther T.C., Pickersgill H.S., Cordes V.C., Goldberg M.W., Allen T.D., Mattaj I.W., Fornerod M. The cytoplasmic filaments of the nuclear pore complex are dispensable for selective nuclear protein import. J Cell Biol. 2002;158:63–77. doi: 10.1083/jcb.200202088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Wang H., Clapham D.E. Conformational changes of the in situ nuclear pore complex. Biophys J. 1999;77:241–247. doi: 10.1016/S0006-3495(99)76885-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Wei X., Henke V.G., Strübing C., Brown E.B., Clapham D.E. Real-time imaging of nuclear permeation by EGFP in single intact cells. Biophys J. 2003;84:1317–1327. doi: 10.1016/S0006-3495(03)74947-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Weis K. Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle. Cell. 2003;112:441–451. doi: 10.1016/S0092-8674(03)00082-5. [DOI] [PubMed] [Google Scholar]
  83. Wozniak R.W., Rout M.P., Aitchison J.D. Karyopherins and kissing cousins. Trends Cell Biol. 1998;8:184–188. doi: 10.1016/S0962-8924(98)01248-3. [DOI] [PubMed] [Google Scholar]
  84. Yang W., Gelles J., Musser S.M. Imaging of singlemolecule translocation through nuclear pore complexes. Proc Natl Acad Sci U S A. 2004;101:12887–12892. doi: 10.1073/pnas.0403675101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Yang W., Musser S.M. Nuclear import time and transport efficiency depend on importin β concentration. J Cell Biol. 2006;174:951–961. doi: 10.1083/jcb.200605053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Yang W., Musser S.M. Visualizing single molecules interacting with nuclear pore complexes by narrow-field epifluorescence microscopy. Methods. 2006;39:316–328. doi: 10.1016/j.ymeth.2006.06.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Yildiz A., Forkey J.N., McKinney S.A., Ha T., Goldman Y.E., Selvin P.R. Myosin V walks hand-over-hand: single fluorophore imaging with 1. localization. Science. 2003;300:2061–2065. doi: 10.1126/science.1084398. [DOI] [PubMed] [Google Scholar]
  88. Yildiz A., Tomishige M., Vale R.D., Selvin P.R. Kinesin walks hand-over-hand. Science. 2004;303:676–678. doi: 10.1126/science.1093753. [DOI] [PubMed] [Google Scholar]
  89. Yokoyama N., Hayashi N., Seki T., Panté N., Ohba T., Nishii K., Kuma K., Hayashida T., Miyata T., Aebi U., et al. A giant nucleopore protein that binds Ran/TC4. Nature. 1995;376:184–188. doi: 10.1038/376184a0. [DOI] [PubMed] [Google Scholar]
  90. Zhuang X. Single-molecule RNA science. Annu Rev Biophys Biomol Struct. 2005;34:399–414. doi: 10.1146/annurev.biophys.34.040204.144641. [DOI] [PubMed] [Google Scholar]

Articles from Protein & Cell are provided here courtesy of Oxford University Press

RESOURCES