TITLE

Chikungunya virus capsid protein contains nuclear import and export signals

AUTHOR(S)
Thomas, Saijo; Rai, Jagdish; John, Lijo; Schaefer, Stephan; Pützer, Brigitte M.; Herchenröder, Ottmar
PUB. DATE
September 2013
SOURCE
Virology Journal;2013, Vol. 10 Issue 1, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family. After autoproteolytic cleavage, the CHIKV capsid protein (CP) is involved in RNA binding and assembly of the viral particle. The monomeric CP is approximately 30 kDa in size and is small enough for passive transport through nuclear pores. Some alphaviruses are found to harbor nuclear localization signals (NLS) and transport of these proteins between cellular compartments was shown to be energy dependent. The active nuclear import of cytoplasmic proteins is mediated by karyopherins and their export by exportins. As nuclear and cytoplasmic trafficking may play a role in the life cycle of CHIKV, we have sought to identify nuclear localization and nuclear export signals in CHIKV CP in a virus-free system. Methods: EGFP-fusion proteins of CHIKV CP and mutants thereof were created and used to monitor their intracellular localization. Binding of cellular proteins was confirmed in pull-down assays with purified CP using co-immuoprecipitation. Nuclear localization was demonstrated in a virus-free system using fluorescence microscopy. Results: Here we show that CHIKV CP is a nuclear-cytoplasmic shuttling protein with an active NLS that binds to karyopherin α (Karα) for its nuclear translocation. We also found that the Karα4 C-terminal NLS binding site is sufficient for this interaction. We further demonstrate that CHIKV CP interacts directly with the export receptor CRM1 to transport this viral protein out of the nucleus via a nuclear export signal (NES). The CHIKV CP NES was mapped between amino acids 143 and 155 of CP. Deduced from in silico analyses we found that the NES has a mode of binding similar to the snurportin-1 CRM1 complex. Conclusions: We were able to show that in a virus-free system that the CHIKV capsid protein contains both, a NLS and a NES, and that it is actively transported between the cytoplasma and the nucleus. We conclude that CHIKV CP has the ability to shuttle via interaction with karyopherins for its nuclear import and, vice versa, by CRM1-dependent nuclear export.
ACCESSION #
90280296

 

Related Articles

  • How to operate a nuclear pore complex by Kap-centric control. Lim, Roderick Y H; Huang, Binlu; Kapinos, Larisa E // Nucleus (1949-1034);2015, Vol. 6 Issue 5, p366 

    Nuclear pore complexes (NPCs) mediate molecular transport between the nucleus and cytoplasm in eukaryotic cells. Tethered within each NPC lie numerous intrinsically disordered proteins known as FG nucleoporins (FG Nups) that are central to this process. Over two decades of investigation has...

  • Cytoplasmic Dynamics of the General Nuclear Import Machinery in Apically Growing Syncytial Cells. Etxebeste, Oier; Villarino, María; Markina-Iñarrairaegui, Ane; Araújo-Bazán, Lidia; Espeso, Eduardo A. // PLoS ONE;Dec2013, Vol. 8 Issue 12, p1 

    Karyopherins are transporters involved in the bidirectional, selective and active transport of macromolecules through nuclear pores. Importin-β1 is the paradigm of karyopherins and, together with its cargo-adapter importin-α, mediates the general nuclear import pathway. Here we show the...

  • Multiple Immune Factors Are Involved in Controlling Acute and Chronic Chikungunya Virus Infection. Poo, Yee Suan; Rudd, Penny A.; Gardner, Joy; Wilson, Jane A. C.; Larcher, Thibaut; Colle, Marie-Anne; Le, Thuy T.; Nakaya, Helder I.; Warrilow, David; Allcock, Richard; Bielefeldt-Ohmann, Helle; Schroder, Wayne A.; Khromykh, Alexander A.; Lopez, José A.; Suhrbier, Andreas // PLoS Neglected Tropical Diseases;Dec2014, Vol. 8 Issue 12, p1 

    The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long...

  • Nuclear organization: Processing at the pore. Schuldt, Alison // Nature Reviews Molecular Cell Biology;Nov2013, Vol. 14 Issue 11, p688 

    The article discusses research being done on the processing at the nuclear pore complex (NPC). It references the study "Integral nuclear pore proteins bind to Pol III-transcribed genes and are required for Pol III transcript processing in C. elegans," by J. Lieb and K. Ikegami in the 2013 issue....

  • Nuclear Export of Pre-Ribosomal Subunits Requires Dbp5, but Not as an RNA-Helicase as for mRNA Export. Neumann, Bettina; Wu, Haijia; Hackmann, Alexandra; Krebber, Heike // PLoS ONE;2/12/2016, Vol. 11 Issue 2, p1 

    The DEAD-box RNA-helicase Dbp5/Rat8 is known for its function in nuclear mRNA export, where it displaces the export receptor Mex67 from the mRNA at the cytoplasmic side of the nuclear pore complex (NPC). Here we show that Dbp5 is also required for the nuclear export of both pre-ribosomal...

  • Remodeling of the Nuclear Envelope and Lamina during Bovine Preimplantation Development and Its Functional Implications. Popken, Jens; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Schmid, Volker J.; Strauss, Axel; Guengoer, Tuna; Zakhartchenko, Valeri; Wolf, Eckhard; Cremer, Thomas // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    The present study demonstrates a major remodeling of the nuclear envelope and its underlying lamina during bovine preimplantation development. Up to the onset of major embryonic genome activation (MGA) at the 8-cell stage nuclei showed a non-uniform distribution of nuclear pore complexes (NPCs)....

  • The transport of integral membrane proteins across the nuclear pore complex. Meinema, Anne C.; Poolman, Bert; Veenhoff, Liesbeth M. // Nucleus (1949-1034);2012, Vol. 3 Issue 4, p1 

    The nuclear envelope protects and organizes the genome. The nuclear pore complexes embedded in the nuclear envelope allow selective transport of macromolecules between the cytosol and nucleoplasm, and as such help to control the low of information from DNA to RNA to proteins. A growing list of...

  • Dissecting the NUP107 complex. González-Aguilera, Cristina; Askjaer, Peter // Nucleus (1949-1034);2012, Vol. 3 Issue 4, Special section p1 

    The Nuclear Pore Complex (NPC) is a fascinating structure whose functional relevance and complexity attract significant interest. Within the NPC, several different subcomplexes interact with each other to form a highly conserved and stable structure. One of these subcomplexes is the NUP107...

  • Assessing the function of the plant nuclear pore complex and the search for specificity. Parry, Geraint // Journal of Experimental Botany;Apr2013, Vol. 64 Issue 4, p833 

    Plant cells encounter a wide variety of molecules that influence their gene expression and development. A key component of most signal transduction pathways involves the regulated movement of molecules into and out of the nucleus. The plant nuclear pore complex (NPC) is a critical controlling...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics