PUBLICATION

In Vivo Optogenetic Phase Transition of an Intrinsically Disordered Protein

Authors
Asakawa, K., Handa, H., Kawakami, K.
ID
ZDB-PUB-230906-67
Date
2024
Source
Methods in molecular biology (Clifton, N.J.)   2707: 257264257-264 (Journal)
Registered Authors
Asakawa, Kazuhide, Kawakami, Koichi
Keywords
ALS, CRY2, IDR, LLPS, Membrane-less organelles, Optogenetics, Phase transition, TDP-43, Zebrafish
MeSH Terms
  • Animals
  • DNA-Binding Proteins
  • Intrinsically Disordered Proteins*/genetics
  • Motor Neurons
  • Optogenetics
  • Zebrafish
PubMed
37668918 Full text @ Meth. Mol. Biol.
Abstract
Proteins containing intrinsically disordered regions (IDRs) control a wide variety of cellular processes by assembly of membrane-less organelles via IDR-mediated liquid-liquid phase separation. Dysregulated IDR-mediated phase transition has been implicated in the pathogenesis of diseases characterized by deposition of abnormal protein aggregates. Here, we describe a method to enhance interactions between the IDRs of the RNA/DNA-binding protein and TAR DNA-binding protein 43 (TDP-43) by light to drive its phase transition in the motor neurons of zebrafish. The optically controlled TDP-43 phase transition in motor neurons, in vivo, provides a unique opportunity to evaluate the impact of dysregulated TDP-43 phase transition on the physiology of motor neurons. This will help to address the etiology of neurodegenerative diseases associated with abnormal TDP-43 phase transition and aggregation, including amyotrophic lateral sclerosis (ALS).
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping