Safeguarding the cell nucleus

Date:
January 31, 2022
Source:
University of Basel
Summary:
The nucleus is guarded by a highly secure door, the so-called
nuclear pore, that controls the transport of substances from the
cytoplasm to the cell nucleus and back. A research group has now
shown that different shuttle proteins occupy the nuclear pore to
prevent unsolicited leakage of molecules. These proteins form an
escape-proof, failsafe mechanism by compensating for one another
to fortify the pore.



FULL STORY ==========================================================================
The nucleus is guarded by a highly secure door, the so-called nuclear
pore, that controls the transport of substances from the cytoplasm to the
cell nucleus and back. A research group at the University of Basel has now shown that different shuttle proteins occupy the nuclear pore to prevent unsolicited leakage of molecules. These proteins form an escape-proof,
failsafe mechanism by compensating for one another to fortify the pore.


==========================================================================
The nuclear pore is responsible for regulating the transport of proteins
from the cytoplasm into the cell nucleus and for ushering RNA out of
it. It works like a molecular sieve that controls the entry and exit
of cargo-carrying shuttle proteins. The molecular sieve interacts with
shuttle proteins, which, like gatekeepers, decide which proteins are
allowed to enter and which are not.

Professor Roderick Lim from the Biozentrum of the University of Basel
aims to resolve this enigmatic selective transport system. His team,
in collaboration with the Swiss Nanoscience Institute, has now examined
three prominent shuttle proteins in human cells and uncovered that their crowding at nuclear pores is important for preventing unwanted leakage
into and out of the nucleus.

The number of shuttle proteins that occupy the pore depends on their concentrations within the cell. However, when one shuttle protein is
reduced, another shuttle protein can take its place to reinforce the
pore. The results of this novel compensation mechanism have now been
published 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, differ in function in terms of the cargo they carry, localization
and concentration," says Dr. Joanna Kalita, first author of the study. The shuttle proteins, which act like gatekeepers at the nuclear pore and
decide which cargoes are allowed to enter the cell nucleus and which
have to be escorted out, reside in the nuclear pore at varying amounts -- depending on their respective concentrations.

When the researchers changed the concentration of one of the shuttle
proteins, the number of the other two proteins that occupied the nuclear
pore also changed. "If the total number of shuttle proteins in the pore
gets reduced, the nuclear pore becomes leaky. Thus, cells rely on a
mechanism that allows the loss of one shuttle protein to be compensated
by the increase of another.

That's how the shuttle proteins safeguard the nuclear pores," says Kalita.

Diseases caused by defective nuclear pores Damage to this biological
security system is detrimental to cells, and has been associated with
cancer and neurodegenerative diseases. Viruses that infect cells,
such as SARS-CoV-2, can also trap these shuttle proteins away from the
nuclear pore to impair its functionality. "This can lead to defects in
the nuclear pore and as a consequence, undesirable substances can freely penetrate the nuclear pores and 'poison' the nucleus.

Conversely, substances important for the cell nucleus are no longer
imported.

Clearly, deeper insights into nuclear pore function will be important for understanding the causes and consequences of defective nuclear transport
with respect to disease," explains Lim.

========================================================================== Story Source: Materials provided by University_of_Basel. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Joanna Kalita, Larisa E. Kapinos, Tiantian Zheng, Chantal Rencurel,
Anton
Zilman, Roderick Y.H. Lim. Karyopherin enrichment and compensation
fortifies the nuclear pore complex against nucleocytoplasmic
leakage.

Journal of Cell Biology, 2022; 221 (3) DOI: 10.1083/jcb.202108107 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220131153313.htm

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