SRCP1 Conveys Resistance to Polyglutamine Aggregation.

Published

Journal Article

The polyglutamine (polyQ) diseases are a group of nine neurodegenerative diseases caused by the expansion of a polyQ tract that results in protein aggregation. Unlike other model organisms, Dictyostelium discoideum is a proteostatic outlier, naturally encoding long polyQ tracts yet resistant to polyQ aggregation. Here we identify serine-rich chaperone protein 1 (SRCP1) as a molecular chaperone that is necessary and sufficient to suppress polyQ aggregation. SRCP1 inhibits aggregation of polyQ-expanded proteins, allowing for their degradation via the proteasome, where SRCP1 is also degraded. SRCP1's C-terminal domain is essential for its activity in cells, and peptides that mimic this domain suppress polyQ aggregation in vitro. Together our results identify a novel type of molecular chaperone and reveal how nature has dealt with the problem of polyQ aggregation.

Full Text

Duke Authors

Cited Authors

  • Santarriaga, S; Haver, HN; Kanack, AJ; Fikejs, AS; Sison, SL; Egner, JM; Bostrom, JR; Seminary, ER; Hill, RB; Link, BA; Ebert, AD; Scaglione, KM

Published Date

  • July 19, 2018

Published In

Volume / Issue

  • 71 / 2

Start / End Page

  • 216 - 228.e7

PubMed ID

  • 30029002

Pubmed Central ID

  • 30029002

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2018.07.008

Language

  • eng

Conference Location

  • United States