Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

A Novel Function of Karyopherin β3 Associated with Apolipoprotein A-I Secretion

  • Chung, Kyung Min (Department of Microbiology and Immunology, Chonbuk National University Medical School) ;
  • Cha, Sun-Shin (Marine Biotechnology Center, Korea Ocean Research and Development Institute) ;
  • Jang, Sung Key (Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology)
  • Received : 2008.03.25
  • Accepted : 2008.04.30
  • Published : 2008.09.30
⟨ Previous Next ⟩

Abstract

Human karyopherin ${\beta}3$, highly homologous to a yeast protein secretion enhancer (PSE1), has often been reported to be associated with a mediator of a nucleocytoplasmic transport pathway. Previously, we showed that karyopherin ${\beta}3$ complemented the PSE1 and KAP123 double mutant. Our research suggested that karyopherin beta has an evolutionary function similar to that of yeast PSE1 and/or KAP 123. In this study, we performed yeast two-hybrid screening to find a protein which would interact with karyopherin ${\beta}3$ and identified apolipoprotein A-I (apo A-I), a secretion protein with a primary function in cholesterol transport. By using in vitro binding assay, co-immunoprecipitation, and colocalization studies, we defined an interaction between karyopherin ${\beta}3$ and apo A-I. In addition, overexpression of karyopherin ${\beta}3$ significantly increased apo A-I secretion. These results suggest that karyopherin ${\beta}3$ plays a crucial role in apo A-I secretion. These findings may be relevant to the study of a novel function of karyopherin ${\beta}3$ and coronary artery diseases associated with apo A-I.

Keywords

Acknowledgement

Supported by : Chonbuk National University

References

  1. Back, S.H., Kim, J.E., Rho, J., Hahm, B., Lee, T.G., Kim, E.E., Cho, J.M., and Jang, S.K. (2000). Expression and purification of an active, full-length hepatitis C viral NS4A. Protein Expr. Purif. 20, 196-206 https://doi.org/10.1006/prep.2000.1301
  2. Banerjee, D., Rodriguez, M., and Rajasekaran, A.K. (1997). Rapid movement of newly synthesized chicken apolipoprotein AI to trans-Golgi network and its secretion in Madin-Darby canine kidney cells. Exp. Cell Res. 235, 334-344 https://doi.org/10.1006/excr.1997.3687
  3. Barter, P.J., and Rye, K.A. (1996). High density lipoproteins and coronary heart disease. Atherosclerosis 121,1-12 https://doi.org/10.1016/0021-9150(95)05675-0
  4. Bayliss, R., Littlewood, T., and Stewart, M. (2000). Structural basis for the interaction between FxFG nucleoporin repeats and importin- beta in nuclear trafficking. Cell 102, 99-108 https://doi.org/10.1016/S0092-8674(00)00014-3
  5. Bednenko, J., Cingolani, G., and Gerace, L. (2003a). Importin beta contains a COOH-terminal nucleoporin binding region important for nuclear transport. J. Cell Biol. 162, 391-401 https://doi.org/10.1083/jcb.200303085
  6. Bednenko, J., Cingolani, G., and Gerace, L. (2003b). Nucleocytoplasmic transport: navigating the channel. Traffic 4, 127-135 https://doi.org/10.1034/j.1600-0854.2003.00109.x
  7. Bordeaux, J., Forte, S., Harding, E., Darshan, M.S., Klucevsek, K., and Moroianu, J. (2006). The l2 minor capsid protein of low-risk human papillomavirus type 11 interacts with host nuclear import receptors and viral DNA. J. Virol. 80, 8259-8262 https://doi.org/10.1128/JVI.00776-06
  8. Brouillette, C.G., and Anantharamaiah, G.M. (1995). Structural models of human apolipoprotein A-I. Biochim. Biophys. Acta 1256, 103-129 https://doi.org/10.1016/0005-2760(95)00018-8
  9. Castro, G., Nihoul, L.P., Dengremont, C., de Geitere, C., Delfly, B., Tailleux, A., Fievet, C., Duverger, N., Denefle, P., Fruchart, J.C., et al. (1997). Cholesterol efflux, lecithin-cholesterol acyltransferase activity, and pre-beta particle formation by serum from human apolipoprotein A-I and apolipoprotein A-I/apolipoprotein A-II transgenic mice consistent with the latter being less effective for reverse cholesterol transport. Biochemistry 36, 2243-2249 https://doi.org/10.1021/bi961191e
  10. Chow, T.Y., Ash, J.J., Dignard, D., and Thomas, D.Y. (1992). Screening and identification of a gene, PSE-1, that affects protein secretion in Saccharomyces cerevisiae. J. Cell Sci. 101, 709-719
  11. Chung, K.M., Lee, J., Kim, J.E., Song, O.K., Cho, S., Lim, J., Seedorf, M., Hahm, B., and Jang, S.K. (2000). Nonstructural protein 5A of hepatitis C virus inhibits the function of karyopherin beta3. J. Virol. 74, 5233-5241 https://doi.org/10.1128/JVI.74.11.5233-5241.2000
  12. Chung, K.M., Nybakken, G.E., Thompson, B.S., Engle, M.J., Marri, A., Fremont, D.H., and Diamond, M.S. (2006). Antibodies against West Nile Virus nonstructural protein NS1 prevent lethal infection through Fc gamma receptor-dependent and - independent mechanisms. J. Virol. 80, 1340-1351 https://doi.org/10.1128/JVI.80.3.1340-1351.2006
  13. Cingolani, G., Petosa, C., Weis, K., and Muller, C.W. (1999). Structure of importin-beta bound to the IBB domain of importin-alpha. Nature 399, 221-229 https://doi.org/10.1038/20367
  14. Cingolani, G., Bednenko, J., Gillespie, M.T., and Gerace, L. (2002). Molecular basis for the recognition of a nonclassical nuclear localization signal by importin beta. Mol. Cell 10, 1345-1353 https://doi.org/10.1016/S1097-2765(02)00727-X
  15. Conti, E. (2002). Structures of importins. Results Probl. Cell Differ. 35, 93-113
  16. Corral-Debrinski, M., Belgareh, N., Blugeon, C., Claros, M.G., Doye, V., and Jacq, C. (1999). Overexpression of yeast karyopherin Pse1p/Kap121p stimulates the mitochondrial import of hydrophobic proteins in vivo. Mol. Microbiol. 31, 1499-1511 https://doi.org/10.1046/j.1365-2958.1999.01295.x
  17. Darshan, M.S., Lucchi, J., Harding, E., and Moroianu, J. (2004). The l2 minor capsid protein of human papillomavirus type 16 interacts with a network of nuclear import receptors. J. Virol. 78, 12179-12188 https://doi.org/10.1128/JVI.78.22.12179-12188.2004
  18. Deane, R., Schafer, W., Zimmermann, H.P., Mueller, L., Gorlich, D., Prehn, S., Ponstingl, H., and Bischoff, F.R. (1997). Ran-binding protein 5 (RanBP5) is related to the nuclear transport factor importin- beta but interacts differently with RanBP1. Mol. Cell. Biol. 17, 5087-5096 https://doi.org/10.1128/MCB.17.9.5087
  19. Deng, T., Engelhardt, O.G., Thomas, B., Akoulitchev, A.V., Brownlee, G.G., and Fodor, E. (2006). Role of ran binding protein 5 in nuclear import and assembly of the influenza virus RNA polymerase complex. J. Virol. 80, 11911-11919 https://doi.org/10.1128/JVI.01565-06
  20. Dynes, J.L., Xu, S., Bothner, S., Lahti, J.M., and Hori, R.T. (2004). The carboxyl-terminus directs TAF(I)48 to the nucleus and nucleolus and associates with multiple nuclear import receptors. J. Biochem. 135, 429-438 https://doi.org/10.1093/jb/mvh051
  21. Ellgaard, L., Molinari, M., and Helenius, A. (1999). Setting the standards: quality control in the secretory pathway. Science 286, 1882-1888 https://doi.org/10.1126/science.286.5446.1882
  22. Forte, T.M., and McCall, M.R. (1994). The role of apolipoprotein A-Icontaining lipoproteins in atherosclerosis. Curr. Opin. Lipidol. 5, 354-364 https://doi.org/10.1097/00041433-199410000-00007
  23. Fruchart, J.C., and Ailhaud, G. (1992). Apolipoprotein A-containing lipoprotein particles: physiological role, quantification, and clinical significance. Clin. Chem. 38, 793-797
  24. Gordon, D.J., Probstfield, J.L., Garrison, R.J., Neaton, J.D., Castelli, W.P., Knoke, J.D., Jacobs, D.R., Jr., Bangdiwala, S., and Tyroler, H.A. (1989). High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 79, 8-15 https://doi.org/10.1161/01.CIR.79.1.8
  25. Gorlich, D. (1997). Nuclear protein import. Curr. Opin. Cell Biol. 9, 412-419 https://doi.org/10.1016/S0955-0674(97)80015-4
  26. Hahm, B., Back, S.H., Lee, T.G., Wimmer, E., and Jang, S.K. (1996). Generation of a novel poliovirus with a requirement of hepatitis C virus protease NS3 activity. Virology 226, 318-326 https://doi.org/10.1006/viro.1996.0659
  27. Hahm, B., Cho, O.H., Kim, J.E., Kim, Y.K., Kim, J.H., Oh, Y.L., and Jang, S.K. (1998). Polypyrimidine tract-binding protein interacts with HnRNP L. FEBS Lett. 425, 401-406 https://doi.org/10.1016/S0014-5793(98)00269-5
  28. Hurtley, S.M., and Helenius, A. (1989). Protein oligomerization in the endoplasmic reticulum. Annu. Rev. Cell Biol. 5, 277-307 https://doi.org/10.1146/annurev.cb.05.110189.001425
  29. Jakel, S., and Gorlich, D. (1998). Importin beta, transportin, RanBP5 and RanBP7 mediate nuclear import of ribosomal proteins in mammalian cells. EMBO J. 17, 4491-4502 https://doi.org/10.1093/emboj/17.15.4491
  30. Kim, J.E., Song, W.K., Chung, K.M., Back, S.H., and Jang, S.K. (1999). Subcellular localization of hepatitis C viral proteins in mammalian cells. Arch. Virol. 144, 329-343 https://doi.org/10.1007/s007050050507
  31. Klausner, R.D., and Sitia, R. (1990). Protein degradation in the endoplasmic reticulum. Cell 62, 611-614 https://doi.org/10.1016/0092-8674(90)90104-M
  32. Kutay, U., Izaurralde, E., Bischoff, F.R., Mattaj, I.W., and Gorlich, D. (1997). Dominant-negative mutants of importin-beta block multiple pathways of import and export through the nuclear pore complex. EMBO J. 16, 1153-1163 https://doi.org/10.1093/emboj/16.6.1153
  33. Lane, C.M., Cushman, I., and Moore, M.S. (2000). Selective disruption of nuclear import by a functional mutant nuclear transport carrier. J. Cell Biol. 151, 321-332 https://doi.org/10.1083/jcb.151.2.321
  34. Lange, A., Mills, R.E., Lange, C.J., Stewart, M., Devine, S.E., and Corbett, A.H. (2007). Classical nuclear localization signals: definition, function, and interaction with importin alpha. J. Biol. Chem. 282, 5101-5105 https://doi.org/10.1074/jbc.R600026200
  35. Lee, S.J., Sekimoto, T., Yamashita, E., Nagoshi, E., Nakagawa, A., Imamoto, N., Yoshimura, M., Sakai, H., Chong, K.T., Tsukihara, T., et al. (2003). The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor. Science 302, 1571-1575 https://doi.org/10.1126/science.1088372
  36. Lee, B.J., Cansizoglu, A.E., Suel, K.E., Louis, T.H., Zhang, Z., and Chook, Y.M. (2006). Rules for nuclear localization sequence recognition by karyopherin beta 2. Cell 126, 543-558 https://doi.org/10.1016/j.cell.2006.05.049
  37. Liang, Y., Kang, C.B., and Yoon, H.S. (2006). Molecular and structure characterization of the domain Hepatitis C virus nonstructural protein 5A. Mol. Cells 22, 13-20
  38. Lodish, H.F. (1988). Transport of secretory and membrane glycoproteins from the rough endoplasmic reticulum to the Golgi. A rate-limiting step in protein maturation and secretion. J. Biol. Chem. 263, 107-2110
  39. Loveland, K.L., Hogarth, C., Szczepny, A., Prabhu, S.M., and Jans, D.A. (2006). Expression of nuclear transport importins beta 1 and beta 3 is regulated during rodent spermatogenesis. Biol. Reprod. 74, 67-74 https://doi.org/10.1095/biolreprod.105.042341
  40. Miettinen, H.E., Jauhiainen, M., Gylling, H., Ehnholm, S., Palomaki, A., Miettinen, T. A., and Kontula, K. (1997). Apolipoprotein AIFIN (Leu159 $\rightarrow$ Arg) mutation affects lecithin cholesterol acyltransferase activation and subclass distribution of HDL but not cholesterol efflux from fibroblasts. Arterioscler Thromb. Vasc. Biol. 17, 3021-3032 https://doi.org/10.1161/01.ATV.17.11.3021
  41. Miller, M., Aiello, D., Pritchard, H., Friel, G., and Zeller, K. (1998). Apolipoprotein A-I(Zavalla) (Leu159 $\rightarrow$ Pro): HDL cholesterol deficiency in a kindred associated with premature coronary artery disease. Arterioscler Thromb. Vasc. Biol. 18, 1242-1247 https://doi.org/10.1161/01.ATV.18.8.1242
  42. Paradise, A., Levin, M.K., Korza, G., and Carson, J.H. (2007). Significant proportions of nuclear transport proteins with reduced intracellular mobilities resolved by fluorescence correlation spectroscopy. J. Mol. Biol. 365, 50-65 https://doi.org/10.1016/j.jmb.2006.09.089
  43. Reid, S.P., Valmas, C., Martinez, O., Sanchez, F.M., and Basler, C.F. (2007). Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin alpha proteins with activated STAT1. J. Virol. 81, 13469-13477 https://doi.org/10.1128/JVI.01097-07
  44. Riddick, G., and Macara, I.G. (2007). The adapter importin-alpha provides flexible control of nuclear import at the expense of efficiency. Mol. Syst. Biol. 3, 118
  45. Rout, M.P., Blobel, G., and Aitchison, J.D. (1997). A distinct nuclear import pathway used by ribosomal proteins. Cell 89, 715-725 https://doi.org/10.1016/S0092-8674(00)80254-8
  46. Schlenstedt, G., Smirnova, E., Deane, R., Solsbacher, J., Kutay, U., Gorlich, D., Ponstingl, H., and Bischoff, F.R. (1997). Yrb4p, a yeast ran-GTP-binding protein involved in import of ribosomal protein L25 into the nucleus. EMBO J. 16, 6237-6249 https://doi.org/10.1093/emboj/16.20.6237
  47. Seedorf, M., and Silver, P.A. (1997). Importin/karyopherin protein family members required for mRNA export from the nucleus. Proc. Natl. Acad. Sci. USA 94, 8590-8595
  48. Seedorf, M., Damelin, M., Kahana, J., Taura, T., and Silver, P.A. (1999). Interactions between a nuclear transporter and a subset of nuclear pore complex proteins depend on Ran GTPase. Mol. Cell. Biol. 19, 1547-1557 https://doi.org/10.1128/MCB.19.2.1547
  49. Shi, S.T., Polyak, S.J., Tu, H., Taylor, D.R., Gretch, D.R., and Lai, M.M. (2002). Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins. Virology 192, 198-210
  50. Uetz, P., Giot, L., Cagney, G., Mansfield, T.A., Judson, R.S., Knight, J.R., Lockshon, D., Narayan, V., Srinivasan, M., Pochart, P., et al. (2000). A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623-627 https://doi.org/10.1038/35001009
  51. Vetter, I.R., Arndt, A., Kutay, U., Gorlich, D., and Wittinghofer, A. (1999). Structural view of the Ran-Importin beta interaction at 2.3 A resolution. Cell 97, 635-646 https://doi.org/10.1016/S0092-8674(00)80774-6
  52. Yaseen, N.R., and Blobel, G. (1997). Cloning and characterization of human karyopherin beta3. Proc. Natl. Acad. Sci. USA 94, 4451-4456
  53. Ying, M., Chen, B., Tian, Y., Hou, Y., Li, Q., Shang, X., Sun, J., Cheng, H., and Zhou, R. (2007). Nuclear import of human sexual regulator DMRT1 is mediated by importin-beta. Biochim. Biophys. Acta 1773, 804-813 https://doi.org/10.1016/j.bbamcr.2007.03.006