Polyphosphate: A Conserved Modifier of Amyloidogenic Processes

Claudia M. Cremers, Daniela Knoefler, Stephanie Gates, Nicholas Martin, Jan Ulrik Dahl, Justine Lempart, Lihan Xie, Matthew R. Chapman, Veronica Galvan, Daniel R. Southworth, Ursula Jakob

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Polyphosphate (polyP), a several billion-year-old biopolymer, is produced in every cell, tissue, and organism studied. Structurally extremely simple, polyP consists of long chains of covalently linked inorganic phosphate groups. We report here the surprising discovery that polyP shows a remarkable efficacy in accelerating amyloid fibril formation. We found that polyP serves as an effective nucleation source for various different amyloid proteins, ranging from bacterial CsgA to human α-synuclein, Aβ1–40/42, and Tau. polyP-associated α-synuclein fibrils show distinct differences in seeding behavior, morphology, and fibril stability compared with fibrils formed in the absence of polyP. In vivo, the amyloid-stimulating and fibril-stabilizing effects of polyP have wide-reaching consequences, increasing the rate of biofilm formation in pathogenic bacteria and mitigating amyloid toxicity in differentiated neuroblastoma cells and C. elegans strains that serve as models for human folding diseases. These results suggest that we have discovered a conserved cytoprotective modifier of amyloidogenic processes.

Original languageEnglish (US)
Pages (from-to)768-780
Number of pages13
JournalMolecular Cell
Volume63
Issue number5
DOIs
StatePublished - Sep 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Cremers, C. M., Knoefler, D., Gates, S., Martin, N., Dahl, J. U., Lempart, J., Xie, L., Chapman, M. R., Galvan, V., Southworth, D. R., & Jakob, U. (2016). Polyphosphate: A Conserved Modifier of Amyloidogenic Processes. Molecular Cell, 63(5), 768-780. https://doi.org/10.1016/j.molcel.2016.07.016