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Heat shock chaperone HSPB1 regulates cytoplasmic TDP-43 phase separation and liquid-to-gel transition

ABSTRACT: While acetylated, RNA binding deficient TDP-43 reversibly phase separates within nuclei into complex droplets (anisosomes) comprised of TDP-43-containing liquid outer shells and liquid centers of HSP70 family chaperones, cytoplasmic aggregates of TDP-43 are hallmarks of multiple neurodegenerative diseases, including ALS. Here we show that transient oxidative stress, proteasome inhibition, or inhibition of HSP70’s ATP-dependent chaperone activity provokes reversible cytoplasmic TDP-43 de-mixing and transition from liquid to gel/solid, independent of RNA binding or stress granules. Proxmity labeling coupled with quantitative mass spectrometry is used to identify that phase separated cytoplasmic TDP-43 is bound by the small heat shock protein HSPB1.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Mixed Disorder As Reaction To Stress

SUBMITTER: Shan Lu

LAB HEAD: John R. Yates III

PROVIDER: PXD035001 | Pride | 2022-08-09

REPOSITORIES: Pride

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			Action	DRS
	20210310_DCSL-TMT-1.csv	Csv
	20210310_DCSL-TMT-1.raw	Raw
	20210310_DCSL-TMT-2.csv	Csv
	20210310_DCSL-TMT-2.raw	Raw
	20210310_DCSL-TMT-3.csv	Csv

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