Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores
Genre
Journal ArticleDate
2020-12-01Author
Mudumbi, KCCzapiewski, R
Ruba, A
Junod, SL
Li, Y
Luo, W
Ngo, C
Ospina, V
Schirmer, EC
Yang, W
Subject
Active Transport, Cell NucleusCell Nucleus
Cytoplasm
Fluorescence Recovery After Photobleaching
HeLa Cells
Humans
Luminescent Proteins
Membrane Proteins
Microscopy, Confocal
Microscopy, FluorescenceNuclear EnvelopeNuclear PoreNucleocytoplasmic Transport ProteinsProtein Transport
Permanent link to this record
http://hdl.handle.net/20.500.12613/4479Metadata
Show full item recordDOI
10.1038/s41467-020-16033-xAbstract
© 2020, The Author(s). 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.Citation to related work
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