Context matters: Cryo-ET reveals the impact of the cellular environment on nuclear pore complex architecture
In this webinar, Anthony Schuller, Ph.D. from UC Berkeley, will present his findings on cryo-electron tomography of the human nuclear pore complex in the native environment.
Full abstract
Nuclear pore complexes (NPCs) create large conduits for transport between the nucleus and cytoplasm across the nuclear envelope. These multi-megadalton structures are composed of more than thirty different nucleoporins, distributed into three main substructures (Inner, Cytoplasmic, and Nucleoplasmic Ring) around the central transport channel. We used cryo-electron tomography on cryo-focused ion beam milled DLD-1 cells to generate a structural model for the human NPC in its native environment. We show that the Inner Ring is substantially widened in the unperturbed cellular environment compared to previous NPC models obtained from purified nuclear envelopes, with an increase of the central channel volume by 75% and a noticeable reorganization of the Nucleoplasmic and Cytoplasmic Rings. Moreover, the NPC membrane exhibits asymmetry around the Inner Ring complex, between its cytoplasmic and nuclear faces. Using targeted degradation of Nup96, a scaffold nucleoporin localized to the Cytoplasmic and Nuclear Rings, we observe the interdependence of each ring in modulating the central channel and maintaining the asymmetric nuclear envelope. Our findings highlight the inherent flexibility of the NPC and strongly suggest that the cellular environment has an under-appreciated influence on NPC dimensions and architecture.
Presenter
Anthony Schuller, Ph.D.
Helen Hay Whitney Postdoctoral Fellow
Schwartz Lab, MIT & Nogales Lab, UC Berkeley