α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster

Elife. 2018 Sep 27:7:e38636. doi: 10.7554/eLife.38636.

Abstract

Damage-associated molecular patterns (DAMPs) are molecules exposed or released by dead cells that trigger or modulate immunity and tissue repair. In vertebrates, the cytoskeletal component F-actin is a DAMP specifically recognised by DNGR-1, an innate immune receptor. Previously we suggested that actin is also a DAMP in Drosophila melanogaster by inducing STAT-dependent genes (<xref ref-type="bibr" rid="bib10">Srinivasan et al., 2016</xref>). Here, we revise that conclusion and report that α-actinin is far more potent than actin at inducing the same STAT response and can be found in trace amounts in actin preparations. Recombinant expression of actin or α-actinin in bacteria demonstrated that only α-actinin could drive the expression of STAT target genes in Drosophila. The response to injected α-actinin required the same signalling cascade that we had identified in our previous work using actin preparations. Taken together, these data indicate that α-actinin rather than actin drives STAT activation when injected into Drosophila.

Keywords: D. melanogaster; DAMP; JAK/STAT pathway; damage-associated molecular pattern; immunology; inflammation; innate immunity; sterile inflammation; tissue injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / administration & dosage
  • Actinin / genetics
  • Actinin / pharmacology*
  • Actins / administration & dosage
  • Actins / genetics
  • Actins / pharmacology*
  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation / drug effects*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • STAT Transcription Factors / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Actins
  • Drosophila Proteins
  • Recombinant Proteins
  • STAT Transcription Factors
  • Actinin