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

Autor:	Mudumbi KC; Department of Biology, Temple University, Philadelphia, PA, 19122, USA. krishna.mudumbi@yale.edu.; Department of Pharmacology, Yale University School of Medicine, New Haven, CT, 06520, USA. krishna.mudumbi@yale.edu.; Yale Cancer Biology Institute, Yale University, West Haven, CT, 06516, USA. krishna.mudumbi@yale.edu., Czapiewski R; The Institute of Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, UK., Ruba A; Department of Biology, Temple University, Philadelphia, PA, 19122, USA., Junod SL; Department of Biology, Temple University, Philadelphia, PA, 19122, USA., Li Y; Department of Biology, Temple University, Philadelphia, PA, 19122, USA., Luo W; Department of Biology, Temple University, Philadelphia, PA, 19122, USA., Ngo C; Department of Biology, Temple University, Philadelphia, PA, 19122, USA., Ospina V; Department of Biology, Temple University, Philadelphia, PA, 19122, USA., Schirmer EC; The Institute of Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, UK. e.schirmer@ed.ac.uk., Yang W; Department of Biology, Temple University, Philadelphia, PA, 19122, USA. weidong.yang@temple.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 May 04; Vol. 11 (1), pp. 2184. Date of Electronic Publication: 2020 May 04.
DOI:	10.1038/s41467-020-16033-x
Abstrakt:	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.
Databáze:	MEDLINE
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