Related Experiment Video
Updated: Sep 18, 2025

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
Published on: February 25, 2022
Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS
Michael E Bekier Ii1, Emile S Pinarbasi1,2, Gopinath Krishnan3
1Department of Neurology and.
None:
Cytoplasmic transactive response DNA-binding protein 43 (TDP43) mislocalization and aggregation are pathological hallmarks of amyotrophic lateral sclerosis (ALS). However, the initial cellular insults that lead to TDP43 mislocalization remain unclear. In this study, we demonstrate that nemo-like kinase (NLK) - a proline-directed serine-threonine kinase - promotes the mislocalization of TDP43 and other RNA-binding proteins by disrupting nuclear import. NLK levels were selectively elevated in neurons exhibiting TDP43 mislocalization in tissues from patients with ALS, and genetic reduction of NLK reduced toxicity in human neuron models of ALS. Our findings suggest that NLK is a promising therapeutic target for neurodegenerative diseases.
More Related Videos
Related Concept Videos
Nuclear Localization Signals and Import
Nuclear Protein Sorting
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Microtubule Instability
Regulation of Nuclear Protein Sorting
Nuclear Export
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
Tail-anchoring of Proteins in the ER Membrane

