Biomedical Research Education & Training
Faculty Member

Wente, Susan, Ph.D.
Senior Associate Dean for Biomedical Sciences
Associate Vice Chancellor for Research
Professor of Cell and Developmental Biology

Lab Url: http://www.mc.vanderbilt.edu/vumcdept/cellbio/wentelab

Phone Number: 615-936-3455

Email Address: susan.wente@vanderbilt.edu

Wente, Susan's picture
Academic history
B. S. , University of Iowa, Iowa City, Iowa
Ph. D., University of California, Berkeley, CA
Postdoctoral, Memorial Sloan Kettering Cancer Center, New York, NY
Postdoctoral, Rockefeller University, New York, NY

Office Address   Mailing Address

3140 MRB III

D3300 Medical Center North 37232-2104


Research Keywords
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

Patient Care Specialty
Not applicable

Research Description
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. Many aspects of this process are poorly understood. At the center of the transport mechanism are the nuclear pore complexes (NPCs), large protein machines embedded in the nuclear envelope and the only known sites for nuclear entry and exit. We use yeast, cultured human cells, and zebrafish model systems to address three broad questions.

(1) How are NPCs assembled? At least 30 different proteins associate in a nuclear envelope pore to form an NPC. Using genetic strategies and GFP-tagged NPCs, we are identifying assembly factors and monitoring NPC dynamics in live cells.

(2) How do proteins and genetic material move through the NPC? By genetic, molecular and biochemical means, we are investigating the mechanism by which transport factors utilize NPC proteins for movement. Studies also focus on elucidating steps in mRNA export, coupling between mRNA export and translation, and roles for inositol polyphosphate signaling in regulating transport.

(3) How do inositol signaling and mRNA export molecules regulate vertebrate development and disease? Using the zebrafish model system, we have made multiple discoveries that open up entirely new areas of investigation.

These basic projects impact human disease in several ways. Proper NPC assembly is required for maintaining transport in rapidly dividing cells (e.g. cancer cells), and for cell division in higher eukaryotes. Cancer cells can also alter gene expression by perturbing nuclear transport. Furthermore, transport factors and NPC proteins are targets for viral inhibition of cell function and mediators of viral RNA export. We predict that analyzing NPC translocation and assembly mechanisms will identify targets for controlling cancer cell growth or viral pathogenesis. Of note, an essential mRNA export factor discovered in our laboratory is linked to a severe form of human motor neuron degeneration, and we are specifically investing effort to reveal this disease mechanism. 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.

Publications
Adams, RL, Wente, SR. Uncovering nuclear pore complexity with innovation. Cell, 152(6), 1218-21, 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

Noble, KN, Tran, EJ, Alc?!zar-Rom?!n, 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

Alc?!zar-Rom?!n, 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

Alc?!zar-Rom?!n, 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

Alc?!zar-Rom?!n, 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, Alc?!zar-Rom?!n, 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


Postdoctoral Position Available
Yes

Postdoctoral Position Details
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.

Updated Date
08/13/2013