Some Inclusion Bodies Protect Cells from Damage by Toxic Misfolded Proteins

JUNQ was shown to be important in managing cellular protein folding quality control, the cellular response to protein aggregation, the formation of prions, and in protecting cells from the toxic effect of aggregation.

In the current paper, which was published in the September 25, 2012, issue of the journal Proceedings of the National Academy of Sciences of the United States of America, the investigators elaborated on the function of JUNQ by presenting direct evidence of a quality control function for JUNQ inclusions in human cultured cells. JUNQ compartments concentrated soluble misfolded proteins together with chaperones and proteasomes, and facilitated their degradation.

The data further showed that the accumulation of insoluble aggregates in the JUNQ inhibited the degradation of other misfolded proteins by sequestering the essential chaperone Hsp70 (heat shock protein 70) and thereby blocking the path of quality control substrates to the proteasome. Rerouting toxic aggregates from the JUNQ to an insoluble polyQ inclusion restored the JUNQ protein degradation function and rescued cell viability.

The authors concluded that toxic and nontoxic inclusions represented different sites of aggregate deposition, with different cell biological properties. They proposed a new approach to treating neurodegenerative diseases that would enhance cellular ability to actively enclose harmful aggregates within protective inclusions, thereby neutralizing the toxic proteins.

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