title: Polyphosphate: A Conserved Modifier of Amyloidogenic Processes.
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.
authors: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Claudia M
authors: CM
authors: Cremers
authors: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Daniela
authors: D
authors: Knoefler
authors: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Stephanie
authors: S
authors: Gates
authors: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Nicholas
authors: N
authors: Martin
authors: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Jan-Ulrik
authors: JU
authors: Dahl
authors: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Justine
authors: J
authors: Lempart
authors: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Lihan
authors: L
authors: Xie
authors: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Matthew R
authors: MR
authors: Chapman
authors: Department of Physiology and The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors: Veronica
authors: V
authors: Galvan
authors: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Daniel R
authors: DR
authors: Southworth
authors: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: ujakob@umich.edu.
authors: Ursula
authors: U
authors: Jakob
mesh_terms: D016229:Amyloid beta-Peptides / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011122:Polyphosphates / Q000737:chemistry / Q000494:pharmacology*; D017510:Protein Folding / Q000187:drug effects; D051844:alpha-Synuclein / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D029968:Escherichia coli Proteins; C054369:MAPT protein, human; D010446:Peptide Fragments; D011122:Polyphosphates; D051844:alpha-Synuclein; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C489688:csgA protein, E coli; D016875:tau Proteins