Safeguarding the cell nucleus

Illustration of the nuclear pore. (Image: Biozentrum, University of Basel)

The nucleus is guarded by a highly secure door, the so-called nuclear pore, thatcontrols the transport of substances from the cytoplasm to the cell nucleus and back. Aresearch group at the University of Basel has now shown that different shuttle proteinsoccupy the nuclear pore to prevent unsolicited leakage of molecules. These proteinsform an escape-proof, failsafe mechanism by compensating for one another to fortifythe pore.

The nuclear pore is responsible for regulating the transport of proteins from the cytoplasminto the cell nucleus and for ushering RNA out of it. It works like a molecular sieve thatcontrols the entry and exit of cargo-carrying shuttle proteins. The molecular sieve interactswith shuttle proteins, which, like gatekeepers, decide which proteins are allowed to enterand which are not.

Illustration of the nuclear pore

Illustration of the nuclear pore. (Animation: Biozentrum, University of Basel)

Argovia-Professor Roderick Lim from the Biozentrum of the University ofBasel aims to resolve this enigmatic selective transport system. Histeam, in collaboration with the Swiss Nanoscience Institute, hasnow examined three prominent shuttle proteins in human cells anduncovered that their crowding at nuclear pores is important forpreventing unwanted leakage into and out of the nucleus.

The number of shuttle proteins that occupy the pore depends ontheir concentrations within the cell. However, when one shuttleprotein is reduced, another shuttle protein can take its place toreinforce the pore. The results of this novel compensation mechanism have now beenpublished in the Journal of Cell Biology.

Interchangeable shuttle proteins safeguard the nuclear pore
“It turns out that the shuttle proteins, although they are from the same receptor family, differin function in terms of the cargo they carry, localization and concentration,” says Dr. JoannaKalita, first author of the study. The shuttle proteins, which act like gatekeepers at the nuclearpore and decide which cargoes are allowed to enter the cell nucleus and which have to beescorted out, reside in the nuclear pore at varying amounts – depending on their respectiveconcentrations.