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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

The Nuclear Pore Complex: Paradoxes and Possibilities

Nuclear pore complexes (NPCs) mediate the traffic of diverse signal-specific cargoes between the cytoplasm and nucleus in eukaryotic cells. This involves numerous intrinsically disordered proteins known as phenylalanine-glycine nucleoporins (FG Nups) that lie physically tethered inside each NPC. Importantly, the FG Nups facilitate the selectivity and speed of cargo-carrying transport receptors (karyopherins or Kaps, specifically importins and exportins) that traverse the NPC. Otherwise, the FG Nups are thought to comprise a barrier that hinders large non-specific molecules from entering the pore. Still after two decades of research, the NPC modus operandi remains unclear because the FG Nups have eluded direct structural visualization inside the pore. Also, little is known as to how multivalent Kap-FG Nup interactions promote rapid NPC translocation. In my talk, I will highlight our efforts to unravel the emergent physical principles that underlie such remarkable biological function. Unexpectedly, our results show that the FG Nups are necessary but insufficient for establishing the NPC barrier. Rather, a surprising finding is that Kaps are essential for both NPC barrier and transport function. In consolidating these results, I will discuss how Kaps might exert control over NPC function - as opposed to the general view that NPCs exert control over the transport of Kaps.

This work is supported by the Swiss National Science Foundation.

References

    Schoch, R.L., Kapinos, L.E. & Lim, R.Y.H. (2012). Nuclear transport receptor binding avidity triggers a self-healing collapse transition in FG-nucleoporin molecular brushes. Proc. Natl. Acad. Sci. USA, 109(42), 16911-6.

    Schleicher, K.D., Dettmer, S.L, Kapinos, L.E, Pagliara, S., Keyser, U.F., Jeney, S. & Lim, R.Y.H. (2014). Selective transport control on molecular velcro made from intrinsically disordered proteins. Nature Nanotechnol., 9(7), 525-30.

    Sakiyama, Y., Mazur, A., Kapinos, L.E. & Lim, R.Y.H. (2016). Spatiotemporal dynamics of the nuclear pore complex transport barrier resolved by high-speed atomic force microscopy. Nature Nanotechnol., 11(8), 719-23.

    Kapinos, L.E., Huang, B., Rencurel, C. & Lim, R.Y.H. (2017). Karyopherins regulate nuclear pore complex barrier and transport function. J. Cell Biol., 216(11), 3609-3624.

Roderick Y.H. Lim

Biozentrum and the Swiss Nanoscience Institute
University of Basel
Basel, Switzerland

Email: roderick.lim@unibas.ch