PQBP5/NOL10 maintains and anchors nucleoli under physiological and osmotic stress conditions

Researchers at Tokyo Medical and Dental University (TMDU) found that PQBP5/NOL10 is an intrinsic disorder protein that supports nucleoli under normal and stressful conditions and binds to polyglutamine disease proteins

Everyone has such a friend, he is the life of the party, bringing people together and keeping everyone connected
.
Now, researchers from Japan have found that a structurally abnormal protein plays a similar role
in combining different proteins together and maintaining their connections and functions.

In one study, researchers at Tokyo Medical and Dental University (TMDU) found that an intrinsic disorder protein (IDP) is critical
for the stability of nucleolar organelles.

Nucleoli are essential for the transcription of ribosome DNA, which encodes key components of ribosomes, which are fundamental organelles
for cell maintenance, differentiation, and stress response.
Many of the proteins that are part of the nucleoli are IDPs, which are prone to deformation and dysfunction
in response to stressors such as temperature changes, hypoxic conditions, or dehydration.

Xiaocen Jin, lead author of the study, said: "We previously found IDP polyglutamine-binding protein 5 (PQBP5), also known as nucleolar protein 10 (NOL10),
in the screening of proteins that bind to polyglutamine (polyQ) sequence in proteins that cause multiq disease.
" PQBP5/NOL10 was later found to be a component of
the nucleoli.
Its integrity is related
to the pathophysiology of neurodegenerative diseases.
”

To determine whether PQBP5/NOL10 is involved in maintaining the structural integrity of the nucleoli, the researchers studied their molecular characteristics, nucleolar sublocalization, relationships with other nucleolar proteins, and stress response
.

"Unexpectedly, we found that PQBP5/NOL10 is the core structural element of the nucleoli, forming a network structure that supports other nucleolar substructures," said
senior author Hitoshi Okazawa.
"More interestingly, unlike other nucleolar proteins that are dispersed into the nucleolar under osmotic stress conditions, PQBP5/NOL10 remains in the nucleola and anchors the recombination
of the nucleolar structure.
"

In addition, the researchers found that PQBP5/NOL10 can essentially be absorbed by polyQ disease proteins, both in cells and in mice
.
This causes the nucleoli to deform or even disappear
.

"Taken together, these findings suggest that PQBP5/NOL10 is a protein necessary to maintain nucleolar structure," Jin said
.

Considering that polyQ proteins form aggregates with dense cores, typically excluding polyQ-binding proteins, PQBP5/NOL10 may initially interact
with the soluble forms of these proteins before being pulled into larger inclusions.
Therefore, aggregation inhibitors that prevent inclusion formation may affect the distribution of PQBP5/NOL10, thereby affecting the stability of nucleoli, providing a new method
for the treatment of multiq diseases.