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Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores
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Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores
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Journal Article
Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores
2020
Overview
Roughly 10% of eukaryotic transmembrane proteins are found on the nuclear membrane, yet how such proteins target and translocate to the nucleus remains in dispute. Most models propose transport through the nuclear pore complexes, but a central outstanding question is whether transit occurs through their central or peripheral channels. Using live-cell high-speed super-resolution single-molecule microscopy we could distinguish protein translocation through the central and peripheral channels, finding that most inner nuclear membrane proteins use only the peripheral channels, but some apparently extend intrinsically disordered domains containing nuclear localization signals into the central channel for directed nuclear transport. These nucleoplasmic signals are critical for central channel transport as their mutation blocks use of the central channels; however, the mutated proteins can still complete their translocation using only the peripheral channels, albeit at a reduced rate. Such proteins can still translocate using only the peripheral channels when central channel is blocked, but blocking the peripheral channels blocks translocation through both channels. This suggests that peripheral channel transport is the default mechanism that was adapted in evolution to include aspects of receptor-mediated central channel transport for directed trafficking of certain membrane proteins.
The contribution of central and peripheral channels of nuclear pores to transport of transmembrane proteins is unclear. Here the authors show that most inner nuclear membrane proteins use only peripheral channels, but some extend nuclear localization signals into the central channel for directed nuclear transport.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/63
/ 631/114
/ 631/57
/ Active Transport, Cell Nucleus
/ Channels
/ Fluorescence Recovery After Photobleaching
/ Humanities and Social Sciences
/ Humans
/ Luminescent Proteins - metabolism
/ Membrane Proteins - metabolism
/ Microscopy, Confocal - methods
/ Microscopy, Fluorescence - methods
/ Mutation
/ Nuclear Envelope - metabolism
/ Nucleocytoplasmic Transport Proteins - metabolism
/ Pores
/ Proteins
/ Science
