title: HSF1-controlled and age-associated chaperone capacity in neurons and muscle cells of C. elegans.
abstract: Protein stability under changing conditions is of vital importance for the cell and under the control of a fine-tuned network of molecular chaperones. Aging and age-related neurodegenerative diseases are directly associated with enhanced protein instability. Employing C. elegans expressing GFP-tagged luciferase as a reporter for evaluation of protein stability we show that the chaperoning strategy of body wall muscle cells and neurons is significantly different and that both are differently affected by aging. Muscle cells of young worms are largely resistant to heat stress, which is directly mediated by the stress response controlled through Heat Shock Transcription Factor 1. During recovery following heat stress the ability to refold misfolded proteins is missing. Young neurons are highly susceptible to chronic heat stress, but show a high potency to refold or disaggregate proteins during subsequent recovery. The particular proteome instability in neurons results from a delayed induction of the heat shock response. In aged neurons protein stability is increased during heat stress, whereas muscle cells show enhanced protein instability due to a deteriorated heat shock response. An efficient refolding activity is absent in both aged tissues. These results provide molecular insights into the differential protein stabilization capacity in different tissues and during aging.
authors.affiliation: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kern
authors.forename: Bianca
authors.initials: B
authors.lastname: Ackermann
authors.forename: Albrecht M
authors.initials: AM
authors.lastname: Clement
authors.forename: Heike
authors.initials: H
authors.lastname: Duerk
authors.forename: Christian
authors.initials: C
authors.lastname: Behl
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D049452:Green Fluorescent Proteins / Q000235:genetics; D008856:Microscopy, Fluorescence; D018832:Molecular Chaperones / Q000502:physiology*; D009132:Muscles / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D020543:Proteome; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D018832:Molecular Chaperones; D020543:Proteome; D014157:Transcription Factors; C474710:heat shock factor-1, C elegans; D049452:Green Fluorescent Proteins