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Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
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Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular
Alessandra Bigi1, Fabrizio Chiti2
1Department of Experimental and Clinical Biomedical Sciences, Section of Biochemistry, University of Florence, Florence, 50134, Italy. alessandra.bigi@unifi.it.
Genome Biology
|January 30, 2026
Summary
TDP-43 protein can form liquid droplets, essential for membraneless organelles, but requires RNA or chaperones. This process may link to neurodegenerative disease inclusions.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Phase separation drives the formation of membraneless organelles.
- TDP-43 protein is implicated in both normal cellular functions and neurodegenerative diseases, forming inclusions.
Purpose of the Study:
- To review the physicochemical basis of TDP-43 liquid-liquid phase separation (LLPS).
- To explore the role of TDP-43 in membraneless organelles and its potential link to pathological inclusions.
Main Methods:
- In vitro biophysical characterization of TDP-43 and its fragments.
- Review of existing literature on TDP-43, LLPS, and neurodegenerative diseases.
Main Results:
- Full-length TDP-43 requires RNA or chaperones to form stable liquid droplets.
- TDP-43 is a component of various membraneless organelles.
Conclusions:
- TDP-43 LLPS is modulated by RNA and chaperones.
- The role of TDP-43-containing organelles as reservoirs for pathological inclusions remains an active area of debate.
Keywords:
Amyotrophic lateral sclerosisAnisosomesFTLD-TDPLATE-NCParaspecklesStress granulesTAR DNA-binding protein 43More Related Videos
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