Edinburgh Research Explorer

Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Open Access permissions

Open

Documents

  • Download as Adobe PDF

    Final published version, 6.75 MB, PDF document

    Licence: Creative Commons: Attribution (CC-BY)

Original languageEnglish
Article number2184
JournalNature Communications
DOIs
Publication statusPublished - 4 May 2020

Abstract

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.

    Research areas

  • transmembrane proteins, nucleocytoplasmic transport, live-cell imaging, single-molecule localization microscopy, single-particle tracking

Download statistics

No data available

ID: 143825974