C9ORF72-derived polyGR polypeptides disrupt passive nucleocytoplasmic transport by tuning protein affinity for the nuclear pore barrier
Daniel A. Solomon, Ryan J. Emenecker, Marie-Therese Salcher-Konrad, Sofia Marina Konstantinidou, O. H. Houghton, Eleanor Wycherley, Seoungjun Lee, Niamh Louise O’Brien, Juan Alcalde, Ines Lourenco Cabaco, Marc‐David Ruepp, Hermann Broder Schmidt, Alex S. Holehouse, Sarah Mizielinska
This study shows how polyGR polypeptides from C9ORF72 disrupt nucleocytoplasmic transport by altering protein affinity for the nuclear pore FG barrier, leading to biphasic transport outcomes and protein aggregation.
bioRxiv · Mar 17, 2026 · PreprintCell Biology