A fundamental question in cell biology is the mechanism by which one structure, the nuclear pore complex, controls all trafficking between the nucleus and the cytoplasm of the eukaryotic cell. Despite this vitally important function, much of the composition of the pores of higher eukaryotes remains unknown, and the molecular mechanism by which the pore engages and translocates substrates is still not understood. Significant progress has been made recently in understanding interactions between pore components and soluble transport factors during import into the nucleus. In contrast, progress is just beginning in the study of factors required for RNA export The Xenopus laevis model provides a uniquely powerful system in which to study RNA export. Using this system, I have shown that the nuclear pore protein, Nup98, is an essential component of multiple RNA export pathways. Additionally, Nup98 specifically interacts with a second protein, Gle2; genetic evidence has linked mutations in the homologs of each of these proteins to defects in polyA+ mRNA export in yeast. The central hypothesis behind this proposal is that the Nup98/Gle2 complex is a key mediator of nuclear export, providing a primary binding site to link export substrates to the transport machinery of the pore. The goals address the specific associations formed by this one subcomplex of the nuclear pore; however it is expected that understanding of this critical interaction will advance our knowledge of the mechanism of nuclear export and provide a framework for characterizing interactions between other export factors and the nuclear pore. The long term goal of this work is a full understanding of how export from the nucleus is conducted through precise cooperation between soluble proteins and the nuclear pore complex.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM059975-05S1
Application #
7036380
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Shapiro, Bert I
Project Start
1999-08-01
Project End
2006-03-31
Budget Start
2003-08-01
Budget End
2006-03-31
Support Year
5
Fiscal Year
2005
Total Cost
$95,818
Indirect Cost
Name
Emory University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Morchoisne-Bolhy, Stéphanie; Geoffroy, Marie-Claude; Bouhlel, Imène B et al. (2015) Intranuclear dynamics of the Nup107-160 complex. Mol Biol Cell 26:2343-56
Chow, Kin-Hoe; Elgort, Suzanne; Dasso, Mary et al. (2014) The SUMO proteases SENP1 and SENP2 play a critical role in nucleoporin homeostasis and nuclear pore complex function. Mol Biol Cell 25:160-8
Xu, Songli; Powers, Maureen A (2013) In vivo analysis of human nucleoporin repeat domain interactions. Mol Biol Cell 24:1222-31
Chatel, Guillaume; Desai, Sachin H; Mattheyses, Alexa L et al. (2012) Domain topology of nucleoporin Nup98 within the nuclear pore complex. J Struct Biol 177:81-9
Cross, Marie K; Powers, Maureen A (2011) Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK. Mol Biol Cell 22:661-72
Xu, Songli; Powers, Maureen A (2010) Nup98-homeodomain fusions interact with endogenous Nup98 during interphase and localize to kinetochores and chromosome arms during mitosis. Mol Biol Cell 21:1585-96
Xu, Songli; Powers, Maureen A (2009) Nuclear pore proteins and cancer. Semin Cell Dev Biol 20:620-30
Ratner, Gary A; Hodel, Alec E; Powers, Maureen A (2007) Molecular determinants of binding between Gly-Leu-Phe-Gly nucleoporins and the nuclear pore complex. J Biol Chem 282:33968-76
Paulillo, Sara M; Powers, Maureen A; Ullman, Katharine S et al. (2006) Changes in nucleoporin domain topology in response to chemical effectors. J Mol Biol 363:39-50
Paulillo, Sara M; Phillips, Erica M; Koser, Joachim et al. (2005) Nucleoporin domain topology is linked to the transport status of the nuclear pore complex. J Mol Biol 351:784-98

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