Nucleocytoplasmic transport: Ran, beta and beyond.

Proteins, RNAs and even large macromolecular complexes are transported into and out of nuclei with remarkable rapidity and specificity. Nucleocytoplasmic transport must therefore be efficient and selective. Characterization of the roles of the importin beta family of transport receptors and of the Ran GTPase has showed how these characteristics can be achieved, but there are many examples of nucleocytoplasmic transport that do not fit this model. Here, we discuss current understanding of various transport mechanisms and evaluate cases in which the molecules and mechanisms underlying nucleocytoplasmic transport are used to carry out important cellular functions in the absence of a nucleus.

[1]  G. Blobel,et al.  The Karyopherin Kap142p/Msn5p Mediates Nuclear Import and Nuclear Export of Different Cargo Proteins , 2001, The Journal of cell biology.

[2]  B. Séraphin,et al.  Dbp5, a DEAD‐box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p , 1999, The EMBO journal.

[3]  M. Hetzer,et al.  An Atp-Dependent, Ran-Independent Mechanism for Nuclear Import of the U1a and U2b′′ Spliceosome Proteins , 2000, Journal of Cell Biology.

[4]  Matthias Mann,et al.  Mtr10p functions as a nuclear import receptor for the mRNA‐binding protein Npl3p , 1998, The EMBO journal.

[5]  Yan Liu,et al.  Dbp5p, a cytosolic RNA helicase, is required for poly(A)+ RNA export , 1998, The EMBO journal.

[6]  Iain W. Mattaj,et al.  Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation , 1999, Nature.

[7]  I. Macara,et al.  Nuclear import of Ran is mediated by the transport factor NTF2 , 1998, Current Biology.

[8]  Mitsuo Sekine,et al.  Snurportin1, an m3G‐cap‐specific nuclear import receptor with a novel domain structure , 1998, The EMBO journal.

[9]  Y. Yoneda.  New steps toward the nucleocytoplasmic traffic of macromolecules. , 2000, Cell structure and function.

[10]  I. Mattaj,et al.  Nucleocytoplasmic transport: the soluble phase. , 1998, Annual review of biochemistry.

[11]  G. Lipowsky,et al.  NTF2 mediates nuclear import of Ran , 1998, The EMBO journal.

[12]  M. Dasso.  Running on Ran Nuclear Transport and the Mitotic Spindle , 2001, Cell.

[13]  G. Blobel,et al.  Nuclear Import of the TATA-binding Protein: Mediation by the Karyopherin Kap114p and a Possible Mechanism for Intranuclear Targeting , 1999, The Journal of cell biology.

[14]  Utz Fischer,et al.  The HIV-1 Rev Activation Domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs , 1995, Cell.

[15]  B. Chait,et al.  The Yeast Nuclear Pore Complex: Composition, Architecture, and Transport Mechanism , 2000 .

[16]  P. Clarke,et al.  Ran GTPase: a master regulator of nuclear structure and function during the eukaryotic cell division cycle? , 2001, Trends in cell biology.

[17]  K Ribbeck,et al.  Kinetic analysis of translocation through nuclear pore complexes , 2001, The EMBO journal.

[18]  M. Rosbash,et al.  The effect of temperature-sensitive RNA mutants on the transcription products from cloned ribosomal protein genes of yeast , 1981, Cell.

[19]  Karsten Weis,et al.  Importin β Is a Mitotic Target of the Small GTPase Ran in Spindle Assembly , 2001, Cell.

[20]  F. Bischoff,et al.  CRM1-mediated Recycling of Snurportin 1 to the Cytoplasm , 1999, The Journal of cell biology.

[21]  H. Le Hir,et al.  The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon–exon junctions , 2000, The EMBO journal.

[22]  E. O’Shea,et al.  Regulation of nuclear localization: a key to a door. , 1999, Annual review of cell and developmental biology.

[23]  P. Silver,et al.  A member of the Ran-binding protein family, Yrb2p, is involved in nuclear protein export. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  E. Conti,et al.  Nucleocytoplasmic transport enters the atomic age. , 2001, Current opinion in cell biology.

[25]  C. Allis,et al.  Chromatin docking and exchange activity enhancement of RCC1 by histones H2A and H2B. , 2001, Science.

[26]  Yixian Zheng,et al.  Role of Importin-β in Coupling Ran to Downstream Targets in Microtubule Assembly , 2001, Science.

[27]  C. Cole,et al.  Dbp5p/Rat8p is a yeast nuclear pore‐associated DEAD‐box protein essential for RNA export , 1998, The EMBO journal.

[28]  S. Vasu,et al.  Nuclear pores and nuclear assembly. , 2001, Current opinion in cell biology.

[29]  Arlen W. Johnson,et al.  Nmd3p Is a Crm1p-Dependent Adapter Protein for Nuclear Export of the Large Ribosomal Subunit , 2000, The Journal of cell biology.

[30]  N. Imamoto,et al.  beta-catenin can be transported into the nucleus in a Ran-unassisted manner. , 1999, Molecular biology of the cell.

[31]  U. Kutay,et al.  The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus , 1997, The EMBO journal.

[32]  E. Noguchi,et al.  Disruption of the YRB2 gene retards nuclear protein export, causing a profound mitotic delay, and can be rescued by overexpression of XPO1/CRM1. , 1999, Journal of biochemistry.

[33]  Angela Bachi,et al.  PHAX, a Mediator of U snRNA Nuclear Export Whose Activity Is Regulated by Phosphorylation , 2000, Cell.

[34]  B. Fahrenkrog,et al.  The RNA export factor Gle1p is located on the cytoplasmic fibrils of the NPC and physically interacts with the FG‐nucleoporin Rip1p, the DEAD‐box protein Rat8p/Dbp5p and a new protein Ymr255p , 1999, The EMBO journal.

[35]  E. Petfalski,et al.  Maturation and Intranuclear Transport of Pre-Ribosomes Requires Noc Proteins , 2001, Cell.

[36]  H. Fried,et al.  Cytoplasmic transport of ribosomal subunits microinjected into the Xenopus laevis oocyte nucleus: a generalized, facilitated process , 1990, The Journal of cell biology.

[37]  J. Yong,et al.  The Y14 protein communicates to the cytoplasm the position of exon–exon junctions , 2001, The EMBO journal.

[38]  B. Blencowe,et al.  REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[39]  D. L. Weeks,et al.  RanGTP-Regulated Interactions of CRM1 with Nucleoporins and a Shuttling DEAD-Box Helicase , 1999, Molecular and Cellular Biology.

[40]  D. Tollervey,et al.  Nuclear Export of 60S Ribosomal Subunits Depends on Xpo1p and Requires a Nuclear Export Sequence-Containing Factor, Nmd3p, That Associates with the Large Subunit Protein Rpl10p , 2001, Molecular and Cellular Biology.

[41]  K. Ramyar,et al.  A Complex of NuMA and Cytoplasmic Dynein Is Essential for Mitotic Spindle Assembly , 1996, Cell.

[42]  William I. Weis,et al.  The Structure of the β-Catenin/E-Cadherin Complex and the Molecular Basis of Diverse Ligand Recognition by β-Catenin , 2001, Cell.

[43]  I. Vernos,et al.  Ran Induces Spindle Assembly by Reversing the Inhibitory Effect of Importin α on TPX2 Activity , 2001, Cell.

[44]  D. Goldfarb,et al.  Pathways for the nuclear transport of proteins and RNAs. , 1991, Trends in cell biology.

[45]  P. Clarke,et al.  Chromatin-independent nuclear envelope assembly induced by Ran GTPase in Xenopus egg extracts. , 2000, Science.

[46]  M. Hetzer,et al.  GTP hydrolysis by Ran is required for nuclear envelope assembly. , 2000, Molecular cell.

[47]  U. Kutay,et al.  Transport between the cell nucleus and the cytoplasm. , 1999, Annual review of cell and developmental biology.

[48]  M. Dasso,et al.  The Ran GTPase regulates mitotic spindle assembly , 1999, Current Biology.

[49]  M. Rout,et al.  The Nuclear Pore Complex as a Transport Machine* , 2001, The Journal of Biological Chemistry.

[50]  R. Reed,et al.  A Ran-independent pathway for export of spliced mRNA , 2000, Nature Cell Biology.

[51]  C. Cole,et al.  Rat8p/Dbp5p is a shuttling transport factor that interacts with Rat7p/Nup159p and Gle1p and suppresses the mRNA export defect of xpo1‐1 cells , 1999, The EMBO journal.

[52]  M. Fornerod,et al.  Nucleocytoplasmic Transport: The Last 200 Nanometers , 1998, Cell.

[53]  E. Hurt,et al.  Yeast genetics to dissect the nuclear pore complex and nucleocytoplasmic trafficking. , 1997, Annual review of genetics.

[54]  R. Kraft,et al.  Importin 13: a novel mediator of nuclear import and export , 2001, The EMBO journal.

[55]  B. Gumbiner,et al.  Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of β-catenin , 1998, Current Biology.

[56]  G. Dreyfuss,et al.  Transport of Proteins and RNAs in and out of the Nucleus , 1999, Cell.

[57]  M. Lindsay,et al.  Ran-Binding Protein 3 Is a Cofactor for Crm1-Mediated Nuclear Protein Export , 2001, The Journal of cell biology.