The rockefeller university

Event Details

Type

Monday Lecture Series

Speaker(s)

Michael Rout, Ph.D., George and Ruby deStevens Professor and head, Laboratory of Cellular and Structural Biology, The Rockefeller University

Speaker bio(s)

Nuclear Pore Complexes (NPCs) mediate the specific and active exchange of transport factors that mediate transport of cognate RNAs and proteins between the cytoplasm and nucleoplasm. We have used an integrative approach to determine structures for the entire 52 MDa yeast NPC, revealing the NPC’s functional elements in unprecedented detail. The NPC is surprisingly modular, consisting of only 30 proteins of the nucleoporin family (Nups), which assemble into relatively rigid higher-order scaffold whose modules are held together by flexible connectors, imbuing the NPC with both strength and flexibility. The scaffold surrounds a central channel from which multiple intrinsically disordered Phe-Gly (FG) repeat motifs project which mediate selective nucleocytoplasmic transport through specific interactions with nuclear transport factors. I will describe our latest findings, including the architectures of the membrane-anchoring domains in the inner ring of the NPC and of the nuclear basket, involved in chromatin organization and processing and transport of mRNPs. I will also describe how the organization of the FG repeats mediates rapid and specific macromolecular transport.

I studied as a graduate student at the Laboratory for Molecular Biology in Cambridge, where I developed techniques for the subfractionation of the yeast nucleus. As a postdoctoral researcher at the Rockefeller University, I studied the Nuclear Pore Complex (NPC), which mediates trafficking between the cytoplasm and nucleoplasm, and also plays key roles in other crucial cellular processes. Using highly enriched yeast NPC fractions for a biochemical and structural approach, we generated the first inventories of its components. This work also demonstrated that there are distinct transport pathways, with many different but partially redundant and overlapping transport pathways all converging at the NPC. In 1997 I started my own laboratory at the Rockefeller University, the main focus of which remains the NPC. The studies of my laboratory and our collaborators have led to the first maps of the three-dimensional architecture of the NPC and the position of all its components, revealing the common evolutionary origins of this structure with vesicle coating proteins, and suggesting a model explaining the overall transport mechanism. We have also studied the kinetics of transport, revealing roles for binding and competition in the mechanism of the NPC, and how multiple and extremely rapid interactions between cargo-carrying transport factors and proteins in the NPC mediate both fast and specific nuclear trafficking. We ultimately aim to generate dynamic maps of the transporting NPC at the atomic and nanosecond level of resolution. We have also applied many of the approaches we have developed and refined to a wide range of cell biology, interactomic and therapeutic studies.

Open to

Campus Only