Molecular determinants of large cargo transport into the nucleus.

ELife
Giulia PaciEdward A Lemke

Abstract

Nucleocytoplasmic transport is tightly regulated by the nuclear pore complex (NPC). Among the thousands of molecules that cross the NPC, even very large (>15 nm) cargoes such as pathogens, mRNAs and pre-ribosomes can pass the NPC intact. For these cargoes, there is little quantitative understanding of the requirements for their nuclear import, especially the role of multivalent binding to transport receptors via nuclear localisation sequences (NLSs) and the effect of size on import efficiency. Here, we assayed nuclear import kinetics of 30 large cargo models based on four capsid-like particles in the size range of 17-36 nm, with tuneable numbers of up to 240 NLSs. We show that the requirements for nuclear transport can be recapitulated by a simple two-parameter biophysical model that correlates the import flux with the energetics of large cargo transport through the NPC. Together, our results reveal key molecular determinants of large cargo import in cells.

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Citations

Jan 27, 2021·Journal of Cell Science·Giulia PaciEdward A Lemke
Aug 3, 2021·Biophysical Journal·Atsushi Matsuda, Mohammad R K Mofrad
Aug 26, 2021·Journal of Cell Science·Giulia PaciEdward A Lemke
Oct 29, 2021·Nature Communications·Jan Andreas RulandUlrich Kubitscheck

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Methods Mentioned

BETA
electron
X-ray
FCS
fluorescence correlation spectroscopy

Software Mentioned

Fiji
Python
IgorPro
Chimera
Malvern

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