Vanderbilt University School of
3140 MRB III
205 Kirkland Hall 37240
Cell biology, nuclear transport, RNA export, organelle assembly, inositol signaling, trafficking, biochemistry, developmental biology, enzyme action, genetics, kinase, knockout, membrane, mutation, neurobiology, protein structure, signal transduction, yeast
Our goal is to understand the mechanism for highly selective, bidirectional exchange of proteins and RNA between the nucleus and cytoplasm. Nucleocytoplasmic trafficking is essential for cell function, and precisely regulated during cell division, differentiation and death. At the center of the transport mechanism are the nuclear pore complexes (NPCs), large protein machines embedded in the nuclear envelope. We use yeast, cultured human cells, and zebrafish model systems to address three key questions:
(1) What are the molecular determinants for regulated transport through the NPC? By genetic, molecular and biochemical means, we investigate how NPC proteins interact with transport receptors and facilitate movement.
(2) How are nuclear and cytoplasmic events simultaneously coupled to control mRNA fate? During stress and disease responses, gene expression pathways adapt to target specific transcripts for rapid export, translation and turnover. We are investigating potential roles for NPC-associated factors in coordinating this response.
(3) How do disruptions in NPC function directly impact human disease and aging? We have recently identified specific NPC transport mechanisms that are perturbed in disease and aging processes. These discoveries have opened up entirely new and exciting areas of investigation.
This deeper understanding of the NPC machinery and its regulation provides key mechanistic insights to many human health challenges. Through thorough analysis of NPC transport factors, we have directly linked precise steps in mRNA export to motor neuron diseases such as ALS and LCCS1, and we have uncovered specific nuclear transport pathways that influence aging. We predict that further elucidation of the mechanisms for NPC transport and regulation will uncover other pathogenic mechanisms and identify druggable targets for controlling human disease. Overall, our future work will continue to integrate our discoveries from the analysis of single cell machineries into the context of multicellular organism development and pathophysiology.
Adams, RL, Terry, LJ, Wente, SR. Nucleoporin FG Domains Facilitate mRNP Remodeling at the Cytoplasmic Face of the Nuclear Pore Complex. Genetics, , , 2014.
Burns, LT, Wente, SR. From hypothesis to mechanism: Uncovering nuclear pore complex links to gene expression. Mol Cell Biol, , , 2014.
Burns, LT, Wente, SR. Casein kinase II Regulation of the Hot1 Transcription Factor Promotes Stochastic Gene Expression. J Biol Chem, , , 2014.
Folkmann, AW, Dawson, TR, Wente, SR. Insights into mRNA export-linked molecular mechanisms of human disease through a Gle1 structure-function analysis. Adv Biol Regul, 54, 74-91, 2014.
Adams, RL, Wente, SR. Uncovering nuclear pore complexity with innovation. Cell, 152(6), 1218-21, 2013.
Folkmann, AW, Collier, SE, Zhan, X, Aditi, , Ohi, MD, Wente, SR. Gle1 functions during mRNA export in an oligomeric complex that is altered in human disease. Cell, 155(3), 582-93, 2013.
Jao, LE, Wente, SR, Chen, W. Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc Natl Acad Sci U S A, , , 2013.
Natalizio, BJ, Wente, SR. Postage for the messenger: designating routes for nuclear mRNA export. Trends Cell Biol, , , 2013.
Burns, LT, Wente, SR. Trafficking to uncharted territory of the nuclear envelope. Curr Opin Cell Biol, 24(3), 341-9, 2012.
Burns, LT, Wente, SR. Nuclear GPS for Interchromosomal Clustering. Dev Cell, 22(6), 1119-20, 2012.
Casey, AK, Dawson, TR, Chen, J, Friederichs, JM, Jaspersen, SL, Wente, SR. Integrity and function of the Saccharomyces cerevisiae spindle pole body depends on connections between the membrane proteins Ndc1, Rtn1, and Yop1. Genetics, 192(2), 441-55, 2012.
Casey, AK, Wente, SR. Nuclear transport: shifting gears in fungal nuclear and cytoplasmic organization. Curr Biol, 22(19), R846-8, 2012.
Jao, LE, Appel, B, Wente, SR. A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization. Development, 139(7), 1316-26, 2012.
Bolger, TA, Wente, SR. Gle1 is a multifunctional DEAD-box protein regulator that modulates Ded1 in translation initiation. J Biol Chem, 286(46), 39750-9, 2011. PMCID:3204050
Folkmann, AW, Noble, KN, Cole, CN, Wente, SR. Dbp5, Gle1-IP6 and Nup159: a working model for mRNP export. Nucleus, 2(6), 540-8, 2011.
Hodge, CA, Tran, EJ, Noble, KN, Alcazar-Roman, AR, Ben-Yishay, R, Scarcelli, JJ, Folkmann, AW, Shav-Tal, Y, Wente, SR, Cole, CN. The Dbp5 cycle at the nuclear pore complex during mRNA export I: dbp5 mutants with defects in RNA binding and ATP hydrolysis define key steps for Nup159 and Gle1. Genes Dev, 25(10), 1052-64, 2011.
Noble, KN, Tran, EJ, Alcazar-Roman, AR, Hodge, CA, Cole, CN, Wente, SR. The Dbp5 cycle at the nuclear pore complex during mRNA export II: nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1. Genes Dev, 25(10), 1065-77, 2011.
Wente, SR. Spatial and temporal impacts on a career in science. Mol Biol Cell, 22(21), 3923-5, 2011. PMCID:3204050
Alcazar-Roman, AR, Bolger, TA, Wente, SR. Control of mRNA export and translation termination by inositol hexakisphosphate requires specific interaction with Gle1. J Biol Chem, 285(22), 16683-92, 2010.
Carmody, SR, Tran, EJ, Apponi, LH, Corbett, AH, Wente, SR. The mitogen-activated protein kinase Slt2 regulates nuclear retention of non-heat shock mRNAs during heat shock-induced stress. Mol Cell Biol, 30(21), 5168-79, 2010. PMCID:2953050
Kelly, SM, Leung, SW, Apponi, LH, Bramley, AM, Tran, EJ, Chekanova, JA, Wente, SR, Corbett, AH. Recognition of polyadenosine RNA by the zinc finger domain of nuclear poly(A) RNA binding protein 2 (Nab2) is required for correct mRNA 3''-end formation. J Biol Chem, , , 2010.
Noble, KN, Wente, SR. Nuclear mRNA on the move. Nat Cell Biol, 12(6), 525-7, 2010.
Sarmah, B, Wente, SR. Zebrafish inositol polyphosphate kinases: new effectors of cilia and developmental signaling. Adv Enzyme Regul, 50(1), 309-23, 2010. PMCID:2836959
Sarmah, B, Wente, SR. Inositol hexakisphosphate kinase-2 acts as an effector of the vertebrate Hedgehog pathway. Proc Natl Acad Sci U S A, 107(46), 19921-6, 2010. PMCID:2993352
Titus, LC, Dawson, TR, Rexer, DJ, Ryan, KJ, Wente, SR. Members of the RSC chromatin-remodeling complex are required for maintaining proper nuclear envelope structure and pore complex localization. Mol Biol Cell, 21(6), 1072-87, 2010. PMCID:2836959
Wente, SR, Rout, MP. The nuclear pore complex and nuclear transport. Cold Spring Harb Perspect Biol, 2(10), a000562, 2010. PMCID:2953050
Zheng, C, Fasken, MB, Marshall, NJ, Brockmann, C, Rubinson, ME, Wente, SR, Corbett, AH, Stewart, M. Structural basis for the function of the Saccharomyces cerevisiae Gfd1 protein in mRNA nuclear export. J Biol Chem, 285(27), 20704-15, 2010.
Beliakova-Bethell, N, Terry, LJ, Bilanchone, V, DaSilva, R, Nagashima, K, Wente, SR, Sandmeyer, S. Ty3 nuclear entry is initiated by viruslike particle docking on GLFG nucleoporins. J Virol, 83(22), 11914-25, 2009. PMCID:2772691
Carmody, SR, Wente, SR. mRNA nuclear export at a glance. J Cell Sci, 122(Pt 12), 1933-7, 2009.
Dawson, TR, Lazarus, MD, Hetzer, MW, Wente, SR. ER membrane-bending proteins are necessary for de novo nuclear pore formation. J Cell Biol, 184(5), 659-75, 2009. PMCID:2686408
Hetzer, MW, Wente, SR. Border control at the nucleus: biogenesis and organization of the nuclear membrane and pore complexes. Dev Cell, 17(5), 606-16, 2009. PMCID:2836959
Sarmah, B, Wente, SR. Dual functions for the Schizosaccharomyces pombe inositol kinase Ipk1 in nuclear mRNA export and polarized cell growth. Eukaryot Cell, 8(2), 134-46, 2009. PMCID:2643608
Terry, LJ, Wente, SR. Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport. Eukaryot Cell, 8(12), 1814-27, 2009. PMCID:2794212
Bolger, TA, Folkmann, AW, Tran, EJ, Wente, SR. The mRNA export factor Gle1 and inositol hexakisphosphate regulate distinct stages of translation. Cell, 134(4), 624-33, 2008. PMCID:2601711
Alcazar-Roman, AR, Wente, SR. Inositol polyphosphates: a new frontier for regulating gene expression. Chromosoma, 117, 1-13, 2007.
Ryan, KJ, Zhou, Y, Wente, SR. The karyopherin kap95 regulates nuclear pore complex assembly into intact nuclear
envelopes in vivo. Mol Biol Cell, 18(3), 886-98, 2007. PMCID:1805111
Sarmah, B, Winfrey, VP, Olson, GE, Appel, B, Wente, SR. A role for the inositol kinase Ipk1 in ciliary beating and length maintenance. Proc Natl Acad Sci U S A, 104(50), 19843-8, 2007. PMCID:2148385
Terry, LJ, Shows, EB, Wente, SR. Crossing the nuclear envelope: hierarchical regulation of nucleocytoplasmic transport. Science, 318(5855), 1412-6, 2007.
Terry, LJ, Wente, SR. Nuclear mRNA export requires specific FG nucleoporins for translocation through the nuclear pore complex. J Cell Biol, 178(7), 1121-32, 2007. PMCID:2064648
Tran, EJ, Bolger, TA, Wente, SR. SnapShot: nuclear transport. Cell, 131(2), 420, 2007.
Tran, EJ, Zhou, Y, Corbett, AH, Wente, SR. The DEAD-box protein Dbp5 controls mRNA export by triggering specific RNA:protein remodeling events. Mol Cell, 28(5), 850-9, 2007.
Alcazar-Roman, AR, Tran, EJ, Guo, S, Wente, SR. Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear
mRNA export. Nat Cell Biol, 8(7), 711-6, 2006.
Hoek, KL, Antony, P, Lowe, J, Shinners, N, Sarmah, B, Wente, SR, Wang, D, Gerstein, RM, Khan, WN. Transitional B cell fate is associated with developmental stage-specific regulation
of diacylglycerol and calcium signaling upon B cell receptor engagement. J Immunol, 177(8), 5405-13, 2006.
Miao, M, Ryan, KJ, Wente, SR. The integral membrane protein Pom34p functionally links nucleoporin subcomplexes. Genetics, 172(3), 1441-57, 2006. PMCID:1456286
Tran, EJ, Wente, SR. Dynamic nuclear pore complexes: life on the edge. Cell, 125(6), 1041-53, 2006.
Kendirgi, F, Rexer, DJ, Alcazar-Roman, AR, Onishko, HM, Wente, SR. Interaction between the shuttling mRNA export factor Gle1 and the nucleoporin
hCG1: a conserved mechanism in the export of Hsp70 mRNA. Mol Biol Cell, 16(9), 4304-15, 2005. PMCID:1196339
Sarmah, B, Latimer, AJ, Appel, B, Wente, SR. Inositol polyphosphates regulate zebrafish left-right asymmetry. Dev Cell, 9(1), 133-45, 2005.
Kiseleva, E, Allen, T D, Rutherford, S, Bucci, M, Wente, SR, Goldberg, MW. Yeast nuclear pore complexes have a cytoplasmic ring and internal filaments. J Struct Biol, 145(3), 272-88, 2004.
Miller, AL, Suntharalingam, M, Johnson, SL, Audhya, A, Emr, SD, Wente, SR. Cytoplasmic inositol hexakisphosphate production is sufficient for mediating
the Gle1-mRNA export pathway. J Biol Chem, 279(49), 51022-32, 2004.
Rayala, HJ, Kendirgi, F, Barry, DM, Majerus, PW, Wente, SR. The mRNA Export Factor Human Gle1 Interacts with the Nuclear Pore Complex Protein Nup155. Mol Cell Proteomics, 3(2), 145-155, 2004.
Strawn, LA, Shen, T, Shulga, N, Goldfarb, DS, Wente, SR. Minimal nuclear pore complexes define FG repeat domains essential for transport. Nat Cell Biol, 6(3), 197-206, 2004.
Suntharalingam, M, Alcazar-Roman, AR, Wente, SR. Nuclear export of the yeast mRNA-binding protein Nab2 is linked to a direct interaction with Gfd1 and to Gle1 function. J Biol Chem, 279, 35384-91, 2004.
Kendirgi, F, Barry, DM, Griffis, ER, Powers, MA, Wente, SR. An essential role for hGle1 nucleocytoplasmic shuttling in mRNA export. J Cell Biol, 160, 1029-40, 2003. PMCID:2172758
Ryan, KJ, McCaffery, JM, Wente, SR. The Ran GTPase cycle is required for yeast nuclear pore complex assembly. J Cell Biol, 160, 1041-53, 2003. PMCID:2172763
Steger, DJ, Haswell, ES, Miller, AL, Wente, SR, OShea, EK. Regulation of chromatin remodeling by inositol polyphosphates. Science, 299, 114-6, 2003. PMCID:1458531
Suntharalingam, M, Wente, SR. Peering through the Pore. Nuclear Pore Complex Structure, Assembly, and Function. Dev Cell, 4, 775-89, 2003.
Bayliss, R, Littlewood, T, Strawn, LA, Wente, SR, Stewart, M. GLFG and FxFG nucleoporins bind to overlapping sites on importin-beta. J Biol Chem, 277, 50597-606, 2002.
Chang, S-C, Miller, AL, Feng, Y, Wente, SR, Majerus, PW. The human homolog of the rat inositol phosphate multikinase is an inositol 1,3,4,6-tetrakisphosphate 5-kinase. J Biol Chem, 277, 43836-43, 2002.
Ryan, KJ, Wente, SR. Isolation and characterization of new Saccharomyces cerevisiae mutants perturbed in nuclear pore complex assembly. BMC Genet, 3, 17, 2002. PMCID:126250
Sondermann, H, Ho, AK, Listenberger, LL, Siegers, K, Moarefi, I, Wente, SR, Hartl, FU, Young, JC. Prediction of novel Bag-1 homologs based on structure/function analysis identifies Snl1p as an Hsp70 co-chaperone in S. cerevisiae. J. Biol. Chem., 277(36), 33220-7, 2002.
Verbsky, JW, Wilson, MP, Kisseleva, MV, Majerus, PW, Wente, SR. The synthesis of inositol hexakisphosphate: Characterization of human inositol 1,3,4,5,6-pentakisphosphate 2-kinase. J. Biol. Chem., 277(35), 31857-62, 2002.
Carvalho, J, Bertram, P G, Wente, S R, Zheng, X F. Phosphorylation regulates the interaction between Gln3p and the nuclear import factor Srp1p. J Biol Chem, 276(27), 25359-65, 2001.
Feng, Y, Wente, S R, Majerus, P W. Overexpression of the inositol phosphatase SopB in human 293 cells stimulates cellular chloride influx and inhibits nuclear mRNA export. Proc Natl Acad Sci U S A, 98(3), 875-9, 2001. PMCID:14677
Strawn, L A, Shen, T, Wente, S R. The GLFG regions of Nup116p and Nup100p serve as binding sites for both Kap95p and Mex67p at the nuclear pore complex. J Biol Chem, 276(9), 6445-52, 2001.
Barry, D M, Wente, S R. Nuclear transport: never-ending cycles of signals and receptors. Essays Biochem, 36, 89-103, 2000.
Ho, A K, Shen, T X, Ryan, K J, Kiseleva, E, Levy, M A, Allen, T D, Wente, S R. Assembly and preferential localization of Nup116p on the cytoplasmic face of the nuclear pore complex by interaction with Nup82p. Mol Cell Biol, 20(15), 5736-48, 2000. PMCID:86051
Ives, EB, Nichols, J, Wente, SR, York, JD. Biochemical and functional characterization of inositol 1,3,4,5, 6-pentakisphosphate 2-kinases. J. Biol. Chem., 275, 36575-83, 2000.
Odom, A. R., Stahlberg, A., Wente, S. R., York, J. D. A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science, 287, 2026-2029, 2000.
Ryan, K and Wente, SR. The nuclear pore complex: a protein machine bridging the nucleus and cytoplasm. Curr. Opin. Cell Biol., 12, 361-371, 2000.
Wente, S. R. Gatekeepers of the nucleus. Science, 288, 1374-1377, 2000.
York, J. D., Odom, A. R., Murphy, R., Ives, E. B., Wente, S. R. A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science, 285, 96-100, 1999.
Bucci, M., Wente, S. R. A novel fluorescence-based genetic strategy identifies mutants of Saccharomyces cerevisiae defective for nuclear pore complex assembly. Mol. Biol. Cell, 9, 2439-2461, 1998.
Ho, A. K., Raczniak, G. A., Ives, E. B., Wente, S. R. The integral membrane protein snl1p is genetically linked to yeast nuclear pore complex function. Mol. Biol. Cell, 9, 355-373, 1998.
Watkins, J. L., Murphy, R., Emtage, J. L., Wente, S. R. The human homologue of Saccharomyces cerevisiae Gle1p is required for poly(A)+ RNA export. Proc. Natl. Acad. Sci. USA, 95, 6779-6784, 1998.
Bucci, M., Wente, S. R. In vivo dynamics of nuclear pore complexes in yeast. J. Cell Biol. , 136, 1185-1199, 1997.
Emtage, J. L., Bucci, M., Watkins, J. L., Wente, S. R. Defining the essential functional regions of the nucleoporin Nup145p. J. Cell Sci., 110, 911-925, 1997.
Iovine, M. K., Wente, S. R. A nuclear export signal in Kap95p is required for both recycling the import factor and interaction with the nucleoporin GLFG repeat regions of Nup116p and Nup100p. J. Cell Biol., 137, 797-811, 1997.
Murphy, R., Watkins, J. L., Wente, S. R. GLE2, a Saccharomyces cerevisiae homologue of the Schizosaccharomyces pombe export factor RAE1, is required for nuclear pore complex structure and function. Mol. Biol. Cell, 7, 1921-1937, 1996.
Murphy, R., Wente, S. R. An RNA-export mediator with an essential nuclear export signal. Nature, 383, 357-360, 1996.
Iovine, M. K., Watkins, J. L., Wente, S. R. The GLFG repetitive region of the nucleoporin Nup116p interacts with Kap95p, an essential yeast nuclear import factor. J. Cell Biol. , 131, 1699-1713, 1995.
Rout, M P, Wente, S R. Pores for thought: nuclear pore complex proteins. Trends Cell Biol, 4(10), 357-65, 1994.
Wente, S. R., Blobel, G. NUP145 encodes a novel yeast glycine-leucine-phenylalanine-glycine (GLFG) nucleoporin required for nuclear envelope structure. J. Cell Biol., 125, 955-969, 1994.
Wente, S. R., Blobel, G. A temperature-sensitive NUP116 null mutant forms a nuclear envelope seal over the yeast nuclear pore complex thereby blocking nucleocytoplasmic traffic. J. Cell Biol. , 123, 275-284, 1993.
Wente, S. R., Rout, M. P. , Blobel, G. A new family of yeast nuclear pore complex proteins. J. Cell Biol. , 119, 705-723, 1992.
Wente, S. R., Schachman, H. K. Different amino acid substitutions at the same position in the nucleotide-binding site of aspartate transcarbamoylase have diverse effects on the allosteric properties of the enzyme. J. Biol. Chem., 266, 20833-20839, 1991.
Wente, S. R., Rosen, O. M. Insulin-receptor approaches to studying protein kinase domain. Diabetes Care, 13, 280-287, 1990.
Wente, S. R., Villalba, R., Schrammm, V. L., Rosen, O. M. Mn2(+)-binding properties of a recombinant protein-tyrosine kinase derived from the human insulin receptor. Proc. Natl. Acad. Sci. USA, 87, 2805-2809, 1990.
Villalba, M., Wente, S. R., Russell, D. S., Ahn, J. C., Reichelderfer, C. F., Rosen, O. M. Another version of the human insulin receptor kinase domain: expression, purification, and characterization. Proc. Natl. Acad. Sci. USA, 86, 7847-7852, 1989.
Wente, S. R., Schachman, H. K. Shared active sites in oligomeric enzymes: model studies with defective mutants of aspartate transcarbamoylase produced by site-directed mutagenesis. Proc. Natl. Acad. Sci. USA, 84, 31-35, 1987.
Robey, E. A., Wente, S. R., Markby, D. W., Flint, A., Yang, Y. R., Schachman, H. K. Effect of amino acid substitutions on the catalytic and regulatory properties of aspartate transcarbamoylase. Proc. Natl. Acad. Sci. USA, 83, 5934-5938, 1986.
My laboratory has funded positions open for excellent scientists at the postdoctoral level who are interested in pursuing the study of nucleocytoplasmic transport. A current curriculum vitae and three letters of reference should be forwarded for consideration.
The scientific projects in my laboratory currently focus on using either yeast S. cerevisiae or mammalian tissue culture, or Xenopus model systems to understand the mechanism of nuclear transport at the molecular level. Toward this goal, the research directives in my laboratory have focused into three subgroups: 1) analyzing the role of nuclear transport factor interactions with the nuclear pore complex, with particular emphasis on either the role of the FG nucleoporins in the general mechanism or the role of the shuttling mRNA export factor Gle1.
2) studying the mechanism of nuclear pore complex assembly and dynamics, with a focus on developing novel fluorescence, genetic, and structural strategies to dissect the pathway of assembly.
3) Understanding how a novel nuclear inositol polyphosphate signaling pathway regulates mRNA export. We speculate that nuclear inositol signaling plays a key role in coordinating mRNA export and gene transcription responses to extracellular stimuli and intracellular cues.
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