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Updated: Jul 17, 2025

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

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Published on: June 15, 2017

In Vivo Optogenetic Phase Transition of an Intrinsically Disordered Protein.

Kazuhide Asakawa¹, Hiroshi Handa², Koichi Kawakami³

¹Laboratory of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Shizuoka, Japan. kasakawa@nig.ac.jp.

Methods in Molecular Biology (Clifton, N.J.)

|September 5, 2023

Summary

This summary is machine-generated.

Researchers developed a light-controlled method to manipulate the phase transition of TAR DNA-binding protein 43 (TDP-43) in zebrafish motor neurons. This technique aids in studying neurodegenerative diseases like ALS linked to TDP-43 aggregation.

Keywords:

ALS CRY2 IDR LLPS Membrane-less organelles Optogenetics Phase transition TDP-43 Zebrafish

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Last Updated: Jul 17, 2025

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

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Published on: June 15, 2017

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Published on: February 25, 2022

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

Area of Science:

Biochemistry and Molecular Biology
Neuroscience
Cell Biology

Background:

Intrinsically disordered regions (IDRs) drive cellular processes through liquid-liquid phase separation, forming membrane-less organelles.
Dysregulation of IDR-mediated phase transitions is linked to protein aggregation in diseases like amyotrophic lateral sclerosis (ALS).
TAR DNA-binding protein 43 (TDP-43) is a key protein implicated in neurodegenerative diseases.

Purpose of the Study:

To develop a method for optically controlling TDP-43 phase transitions in vivo.
To investigate the physiological impact of dysregulated TDP-43 phase transition in motor neurons.
To provide a model system for studying the etiology of TDP-43-associated neurodegenerative diseases.

Main Methods:

Utilized light to enhance interactions between IDRs of RNA/DNA-binding proteins and TDP-43.
Induced and controlled TDP-43 liquid-liquid phase separation in zebrafish motor neurons.
Established an in vivo model for observing TDP-43 phase transition dynamics.

Main Results:

Successfully demonstrated light-inducible TDP-43 phase transition in zebrafish motor neurons.
Developed a novel tool for precise, non-invasive manipulation of protein phase separation in living organisms.
Created a platform for evaluating the consequences of aberrant TDP-43 aggregation.

Conclusions:

Optically controlled TDP-43 phase transition offers a powerful in vivo approach to study neurodegenerative disease mechanisms.
This method facilitates research into the role of TDP-43 aggregation in diseases such as ALS.
Understanding TDP-43 phase transition dynamics is crucial for developing therapeutic strategies for related neurodegenerative disorders.