The ER Hsp70 Hspa13 Redirects an Amyloidogenic Protein to Aggregation

Abstract

The conserved ER Hsp70 chaperone Hspa13/STCH is implicated in cancer and neurodegenerative diseases. While other Hsp70 proteins maintain proteostasis by promoting folding, degradation, or disaggregation of misfolded protein, the biological function of Hspa13 is unknown, in part because it lacks the substrate‐binding domain required for the function of other members of the Hsp70 class. We investigated the intracellular effect of Hspa13 overexpression on the kinetically stable, amyloidogenic protein transthyretin (TTR), finding that Hspa13 promotes the partitioning of TTR into high‐molecular weight, detergent‐resistant aggregates inside living cells. This function is ATP‐independent and opposed by the ER nucleotide exchange factor HYOU1, but unaffected by the primary ER Hsp70 BiP. These results suggest a role for Hspa13 in maintaining ER proteostasis by regulating the aggregation of amyloidogenic protein in the secretory pathway.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.