Chaperone-mediated formation of shell-like TDP-43 condensates

• Main Author: Kong, Jian Hua
• Other Authors: Choe Young Jun
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2022
• Subjects: Science::Biological sciences::Molecular biology
• Online Access: https://hdl.handle.net/10356/156869
• Institution: Nanyang Technological University

Transactivation response element DNA binding protein 43 (TDP-43), an RNA-binding protein is the major component of inclusion bodies in patients afflicted with Amyotrophic Lateral Sclerosis (ALS). A recent study established that a compromise in RNA-binding capacity of TDP-43, resulting from post-translational modifications or ALS-causing mutations, confers TDP-43 the ability to de-mix into intranuclear liquid spherical shells with a liquid core. The major chaperone, Heat shock protein 70 (Hsp70), was reported to be enriched within the liquid core and pivotal in maintenance of the shell structure. To examine the presence of other chaperones in the core of the TDP-43 shell. Interestingly, reduced function of the Hsp70 system abrogated the shell formation. It is very likely that other chaperones are also enriched in the TDP-43 shell-like structures. Further investigation into how chaperones mediate TDP-43 phase separation could illuminate the molecular basis for ALS.