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University of Rochester

1. Liu, Li-Ka (1977 - ). A direct role of the nuclear pore complex in the regulation of nuclear import pathways.

Degree: PhD, 2012, University of Rochester

Multiple karyopherins (Kaps) ferry nuclear localization signal (NLS)-bearing cargos across the nuclear pore complex (NPC). Kaps bind to the NPC via the FG-domains of nucleoporins such as Nup42. We have found that Nup42 governs a unique stress response that differentially controls import mediated by Kap95/60 and Kap104. In vivo kinetic analyses show that Kap95/60 and Kap104 compete for limiting docking sites at Nup42. Binding to Nup42 is the rate-limiting step in import, since the import rates of Kap95/60 and Kap104 NLS-cargos are faster in nup42DFG cells. Nup42 collaborates with the Hsp70s Ssa1/Ssa2 (but not Ssa3/Ssa4) and the co-chaperone Swa2 to differentially control nuclear targeting by Kap95/60 and Kap104. Specifically, Kap95/60 import is favored over Kap104 import when Ssa1/Ssa2 levels are high, such as in response to heat shock, ethanol stress or nutrient depletion. In contrast, Kap104 import is favored when the free Hsp70 pool is depleted, for example, by sequestration into Huntingtin polyQ protein aggregates. Kap123-mediated import rates are unaffected by this regulatory circuit. We suggest that Nup42 is a Kap-specific gatekeeper that controls import rates in response to proteostatic stress. In addition to the Ssa1/Swa2 that is required for Nup42- dependent regulatory circuit, we demonstrated that Ede1, a scaffold protein of endocytosis, is also required. Ede1 is involved in the Nup42-dependent regulatory circuit via a NPF-EH interaction with Nup42. This Nup42-Ede1 interaction is required for Nup42-dependent differential control of Kap95/60 and Kap104 imports.

Subjects/Keywords: Nuclear pore complex (NPC); Nucleoporin; Karyopherin; Nuclear import; Kap95; Kap104; Nup42; Heat shock protein

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Liu, L. (. -. ). (2012). A direct role of the nuclear pore complex in the regulation of nuclear import pathways. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/18646

Chicago Manual of Style (16th Edition):

Liu, Li-Ka (1977 - ). “A direct role of the nuclear pore complex in the regulation of nuclear import pathways.” 2012. Doctoral Dissertation, University of Rochester. Accessed July 23, 2019. http://hdl.handle.net/1802/18646.

MLA Handbook (7th Edition):

Liu, Li-Ka (1977 - ). “A direct role of the nuclear pore complex in the regulation of nuclear import pathways.” 2012. Web. 23 Jul 2019.

Vancouver:

Liu L(-). A direct role of the nuclear pore complex in the regulation of nuclear import pathways. [Internet] [Doctoral dissertation]. University of Rochester; 2012. [cited 2019 Jul 23]. Available from: http://hdl.handle.net/1802/18646.

Council of Science Editors:

Liu L(-). A direct role of the nuclear pore complex in the regulation of nuclear import pathways. [Doctoral Dissertation]. University of Rochester; 2012. Available from: http://hdl.handle.net/1802/18646

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