Forced entry into the nucleus

Abstract

Transport of macromolecules into and out of the nucleus is regulated by the nuclear pore complex (NPC). A new study shows that mechanical force applied on the nucleus affects the transport rates across the NPC’s diffusion barrier, modulating the nuclear localization of certain cargos, including some transcriptional regulators. These results suggest that mechanosensing by the NPC could be a general mechanism for triggering signaling pathways in response to mechanical force exerted on the cell.

Fig. 1 |. Mechanical tuning of nucleocytoplasmic transport.

(A) Active karyopherin (Kap)-mediated and passive transport pathways through the central transport channel of the nuclear pore complex (NPC). In the classical import pathway, the cargo’s NLS binds to an adaptor α-Kap (importin-α), displacing its autoinhibitory importin-β-binding (IBB) α-helix, which binds to an import β-Kap (importin-β); the ternary import complex shuttles across the diffusion barrier and disassembles upon arrival in the nucleus by Ran(GTP) binding. In the export pathway, NES-presenting cargo forms a ternary complex with Ran(GTP) and an export β-Kap (exportin) that shuttles across the diffusion barrier; in the cytoplasm, Ran’s GTPase activity is stimulated to disassemble the complex. (B) Cryo-ET reconstructions of the constricted and dilated human NPCs interpreted by docking crystal and single particle cryo-EM structures of its nucleoporin protein subunits^,,.