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Title page for ETD etd-12052008-104202


Type of Document Dissertation
Author Terry, Laura Jennings
URN etd-12052008-104202
Title FG nucleoporins coordinate multiple transport pathways through the nuclear pore complex
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
James G. Goldenring Committee Chair
Byeong J. Cha Committee Member
Katherine L. Friedman Committee Member
Susan R. Wente Committee Member
Todd R. Graham Committee Member
Keywords
  • Nuclear proteins
  • cell biology
  • mRNA
  • nucleus
  • yeast
  • nuclear pore
  • transport
  • Nuclear membranes
  • RNA -- Physiological transport
Date of Defense 2008-11-20
Availability unrestricted
Abstract
Transport of nucleic acids and proteins between the nucleus and cytoplasm occurs exclusively through nuclear pore complexes (NPCs), large transport channels embedded in the nuclear envelope. Molecules larger than ~40kDa are largely excluded from moving through the NPC unless bound by a specialized transport receptor. Cargo macromolecules bind a transport receptor, which in turn interacts with a subset of NPC proteins containing phenylalanine-glycine (FG) repeat domains. Trafficking of a transport receptor-cargo complex through the NPC requires stochastic, low-affinity interactions between the transport receptor and FG repeat domains. More than a third of the ~30 NPC proteins harbor FG repeat domains, and each FG repeat domain potentially serves as a binding site for transport receptors at intermediate points in nucleocytoplasmic transport. Whether each of the ~15 transport receptors in yeast preferentially binds a subset of these FG domains is unresolved. In this study, we used genetic strategies in Saccharomyces cerevisiae to systematically delete (∆) combinations of FG domains. We assayed these FG∆ mutants for defects in trafficking of several different transport receptors, including a specific focus on messenger RNA (mRNA) export. We found that mRNA export and specific protein import receptors require different subsets of FG domains. This result indicates that there are multiple transport pathways through the NPC, each of which is defined by preferential binding of a transport receptor to a subset of FG domains. Additionally, we found that FG domains located on the nuclear side of the NPC contribute to recruiting the mRNA export receptor to the NPC. Further, FG domains positioned on the cytoplasmic side of the NPC might regulate terminal events in mRNA export. As a whole, these results suggest that each FG domain might play a regulatory role in mediating efficient movement of specific transport receptors through the NPC.
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