A Damage Sensor Associated with the Cuticle Coordinates Three Core Environmental Stress Responses in Caenorhabditis elegans

Genetics. 2018 Apr;208(4):1467-1482. doi: 10.1534/genetics.118.300827. Epub 2018 Feb 27.

Abstract

Extracellular matrix barriers and inducible cytoprotective genes form successive lines of defense against chemical and microbial environmental stressors. The barrier in nematodes is a collagenous extracellular matrix called the cuticle. In Caenorhabditis elegans, disruption of some cuticle collagen genes activates osmolyte and antimicrobial response genes. Physical damage to the epidermis also activates antimicrobial responses. Here, we assayed the effect of knocking down genes required for cuticle and epidermal integrity on diverse cellular stress responses. We found that disruption of specific bands of collagen, called annular furrows, coactivates detoxification, hyperosmotic, and antimicrobial response genes, but not other stress responses. Disruption of other cuticle structures and epidermal integrity does not have the same effect. Several transcription factors act downstream of furrow loss. SKN-1/Nrf and ELT-3/GATA are required for detoxification, SKN-1/Nrf is partially required for the osmolyte response, and STA-2/Stat and ELT-3/GATA for antimicrobial gene expression. Our results are consistent with a cuticle-associated damage sensor that coordinates detoxification, hyperosmotic, and antimicrobial responses through overlapping, but distinct, downstream signaling.

Keywords: antimicrobial response; collagen; damage sensor; detoxification; osmotic stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Environment*
  • Extracellular Matrix / metabolism
  • Gene Expression Profiling
  • Gene-Environment Interaction
  • High-Throughput Nucleotide Sequencing
  • Inactivation, Metabolic / genetics
  • Osmosis
  • Stress, Physiological*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome
  • Transgenes

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Transcription Factors
  • skn-1 protein, C elegans