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In Vivo Optogenetic Phase Transition of an Intrinsically Disordered Protein

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Zebrafish

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2707))

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).

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Acknowledgments

This work was supported by SERIKA FUND (K.A.), KAKENHI Grant numbers JP19K06933 (K.A.) and JP20H05345 (K.A.).

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Correspondence to Kazuhide Asakawa .

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© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Asakawa, K., Handa, H., Kawakami, K. (2024). In Vivo Optogenetic Phase Transition of an Intrinsically Disordered Protein. In: Amatruda, J.F., Houart, C., Kawakami, K., Poss, K.D. (eds) Zebrafish. Methods in Molecular Biology, vol 2707. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3401-1_17

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  • DOI: https://doi.org/10.1007/978-1-0716-3401-1_17

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3400-4

  • Online ISBN: 978-1-0716-3401-1

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