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).
CITATION STYLE
Asakawa, K., Handa, H., & Kawakami, K. (2024). In Vivo Optogenetic Phase Transition of an Intrinsically Disordered Protein. In Methods in Molecular Biology (Vol. 2707, pp. 257–264). Humana Press Inc. https://doi.org/10.1007/978-1-0716-3401-1_17
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