Author response: Molecular determinants of large cargo transport into the nucleus

The liquid state of FG-nucleoporins mimics permeability barrier properties of nuclear pore complexes

Nuclear pore complexes form a permeability barrier in vivo that regulates nucleocytoplasmic transport. Here, the authors present a microfluidic device that couples rapid liquid–liquid phase separation of nucleoporins with direct optical interrogation. Freshly formed liquid nucleoporin droplets mimic permeability barrier properties of NPCs.

Molecular determinants of large cargo transport into the nucleus

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 requireme…

Cargo transport through the nuclear pore complex at a glance.

ABSTRACT Bidirectional transport of macromolecules across the nuclear envelope is a hallmark of eukaryotic cells, in which the genetic material is compartmentalized inside the nucleus. The nuclear pore complex (NPC) is the major gateway to the nucleus and it regulates nucleocytoplasmic transport, which is key to processes including transcriptional regulation and cell cycle control. Accordingly, components of the nuclear transport machinery are often found to be dysregulated or hijacked in diseases. In this Cell Science at a Glance article and accompanying poster, we provide an overview of our current understanding of cargo transport through the NPC, from the basic transport signals and mach…