Nuclear import receptors directly bind to arginine-rich dipeptide repeat proteins and suppress their pathological interactions

S Hutten, S Usluer, B Bourgeois, F Simonetti, HM Odeh… - Cell reports, 2020 - cell.com
Nuclear import receptors, also called importins, mediate nuclear import of proteins and
chaperone aggregation-prone cargoes (eg, neurodegeneration-linked RNA-binding …

C9orf72 arginine-rich dipeptide repeat proteins disrupt karyopherin-mediated nuclear import

LR Hayes, L Duan, K Bowen, P Kalab, JD Rothstein - Elife, 2020 - elifesciences.org
Disruption of nucleocytoplasmic transport is increasingly implicated in the pathogenesis of
neurodegenerative diseases, including ALS caused by a C9orf72 hexanucleotide repeat …

Nuclear RNA binding regulates TDP-43 nuclear localization and passive nuclear export

L Duan, BL Zaepfel, V Aksenova, M Dasso… - Cell reports, 2022 - cell.com
Nuclear clearance of the RNA-binding protein TDP-43 is a hallmark of neurodegeneration
and an important therapeutic target. Our current understanding of TDP-43 …

Nuclear import receptors are recruited by FG-nucleoporins to rescue hallmarks of TDP-43 proteinopathy

B Khalil, D Chhangani, MC Wren, CL Smith… - Molecular …, 2022 - Springer
Background Cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43
(TDP-43) is a hallmark of the amyotrophic lateral sclerosis and frontotemporal dementia …

Recognition of the TDP-43 nuclear localization signal by importin α1/β

SG Doll, H Meshkin, AJ Bryer, F Li, YH Ko… - Cell reports, 2022 - cell.com
Cytoplasmic mislocalization of the TAR-DNA binding protein of 43 kDa (TDP-43) leads to
large, insoluble aggregates that are a hallmark of amyotrophic lateral sclerosis and …

Nuclear import impairment causes cytoplasmic trans-activation response DNA-binding protein accumulation and is associated with frontotemporal lobar degeneration

AL Nishimura, V Župunski, C Troakes, C Kathe… - Brain, 2010 - academic.oup.com
Trans-activation response DNA-binding protein (TDP-43) accumulation is the major
component of ubiquitinated protein inclusions found in patients with amyotrophic lateral …

C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers

H Nanaura, H Kawamukai, A Fujiwara… - Nature …, 2021 - nature.com
Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also
modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic …

Active nuclear import and passive nuclear export are the primary determinants of TDP-43 localization

ES Pinarbasi, T Cağatay, HYJ Fung, YC Li… - Scientific reports, 2018 - nature.com
Abstract ALS (Amyotrophic Lateral Sclerosis) is a neurodegenerative disease characterized
by the redistribution of the RNA binding protein TDP-43 in affected neurons: from …

Loss of C9orf72 perturbs the Ran-GTPase gradient and nucleocytoplasmic transport, generating compositionally diverse Importin β-1 granules

P McGoldrick, A Lau, Z You, TM Durcan, J Robertson - Cell Reports, 2023 - cell.com
A hexanucleotide (GGGGCC) n repeat expansion in C9orf72 causes amyotrophic lateral
sclerosis (ALS) and frontotemporal dementia (FTD), eliciting toxic effects through generation …

Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72 …

S Saberi, JE Stauffer, J Jiang, SD Garcia, AE Taylor… - Acta …, 2018 - Springer
Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of
amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are …