bims-nucpor 2024-02-25 papers

Issue of 2024‒02‒25
two papers selected by
Sara Mingu, Johannes Gutenberg University

Elife. 2024 Feb 20. pii: RP87174. [Epub ahead of print]12

Diameter dependence of transport through nuclear pore complex mimics studied using optical nanopores.

Nils Klughammer, Anders Barth, Maurice Dekker, Alessio Fragasso, Patrick R Onck, Cees Dekker.

The nuclear pore complex (NPC) regulates the selective transport of large biomolecules through the nuclear envelope. As a model system for nuclear transport, we construct NPC mimics by functionalizing the pore walls of freestanding palladium zero-mode waveguides with the FG-nucleoporin Nsp1. This approach enables the measurement of single-molecule translocations through individual pores using optical detection. We probe the selectivity of Nsp1-coated pores by quantitatively comparing the translocation rates of the nuclear transport receptor Kap95 to the inert probe BSA over a wide range of pore sizes from 35 nm to 160 nm. Pores below 55 ± 5 nm show significant selectivity that gradually decreases for larger pores. This finding is corroborated by coarse-grained molecular dynamics simulations of the Nsp1 mesh within the pore, which suggest that leakage of BSA occurs by diffusion through transient openings within the dynamic mesh. Furthermore, we experimentally observe a modulation of the BSA permeation when varying the concentration of Kap95. The results demonstrate the potential of single-molecule fluorescence measurements on biomimetic NPCs to elucidate the principles of nuclear transport.

Keywords: biomimetics; intrinsically disordered proteins; none; nuclear pore complex; nucleocytoplasmic transport; physics of living systems; single-molecule fluorescence; solid-state nanopores

DOI: https://doi.org/10.7554/eLife.87174

Nucleus. 2024 Dec;15(1): 2314297

Nuclear pore dysfunction and disease: a complex opportunity.

Charlotte M Fare, Jeffrey D Rothstein.

The separation of genetic material from bulk cytoplasm has enabled the evolution of increasingly complex organisms, allowing for the development of sophisticated forms of life. However, this complexity has created new categories of dysfunction, including those related to the movement of material between cellular compartments. In eukaryotic cells, nucleocytoplasmic trafficking is a fundamental biological process, and cumulative disruptions to nuclear integrity and nucleocytoplasmic transport are detrimental to cell survival. This is particularly true in post-mitotic neurons, where nuclear pore injury and errors to nucleocytoplasmic trafficking are strongly associated with neurodegenerative disease. In this review, we summarize the current understanding of nuclear pore biology in physiological and pathological contexts and discuss potential therapeutic approaches for addressing nuclear pore injury and dysfunctional nucleocytoplasmic transport.

Keywords: Neurodegenerative disease; nuclear envelope; nuclear pore complex; nucleocytoplasmic transport; nucleoporin; therapeutics

DOI: https://doi.org/10.1080/19491034.2024.2314297