Nuclear Pore Complex Is Able to Transport Macromolecules with Diameters of ∼39 nm

TLDR

Bidirectional transport between nucleus and cytoplasm occurs through nuclear pore complexes via a signal‑mediated mechanism driven by nuclear localization signals on cargoes. The study aims to determine the maximum size of macromolecules that can be transported by this signal‑mediated mechanism. Gold particles of varying diameters coated with cargo‑receptor complexes were used to probe the size limit of NPC translocation. Cargo‑receptor‑gold complexes up to ~39 nm in diameter were successfully translocated, showing that macromolecules larger than the previously assumed 26 nm NPC diameter, such as 32–36 nm hepatitis B virus nucleocapsids, can cross the pore without disassembly.

Abstract

Bidirectional transport of macromolecules between the nucleus and the cytoplasm occurs through the nuclear pore complexes (NPCs) by a signal-mediated mechanism that is directed by targeting signals (NLSs) residing on the transported molecules or "cargoes." Nuclear transport starts after interaction of the targeting signal with soluble cellular receptors. After the formation of the cargo-receptor complex in the cytosol, this complex crosses the NPC. Herein, we use gold particles of various sizes coated with cargo-receptor complexes to determine precisely how large macromolecules crossing the NPC by the signal-mediated transport mechanism could be. We found that cargo-receptor-gold complexes with diameter close to 39 nm could be translocated by the NPC. This implies that macromolecules much larger than the assumed functional NPC diameter of 26 nm can be transported into the karyoplasm. The physiological relevance of this finding was supported by the observation that intact nucleocapsids of human hepatitis B virus with diameters of 32 and 36 nm are able to cross the nuclear pore without disassembly.