Age-Onset Phosphorylation of a Minor Actin Variant Promotes Intestinal Barrier Dysfunction

Nathan Egge, Sonja L.B. Arneaud, Pauline Wales, Melina Mihelakis, Jacob McClendon, Rene Solano Fonseca, Charles Savelle, Ian Gonzalez, Atossa Ghorashi, Sivaramakrishna Yadavalli, William J. Lehman, Hamid Mirzaei, Peter M. Douglas

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Age-associated decay of intercellular interactions impairs the cells’ capacity to tightly associate within tissues and form a functional barrier. This barrier dysfunction compromises organ physiology and contributes to systemic failure. The actin cytoskeleton represents a key determinant in maintaining tissue architecture. Yet, it is unclear how age disrupts the actin cytoskeleton and how this, in turn, promotes mortality. Here, we show that an uncharacterized phosphorylation of a low-abundant actin variant, ACT-5, compromises integrity of the C. elegans intestinal barrier and accelerates pathogenesis. Age-related loss of the heat-shock transcription factor, HSF-1, disrupts the JUN kinase and protein phosphatase I equilibrium which increases ACT-5 phosphorylation within its troponin binding site. Phosphorylated ACT-5 accelerates decay of the intestinal subapical terminal web and impairs its interactions with cell junctions. This compromises barrier integrity, promotes pathogenesis, and drives mortality. Thus, we provide the molecular mechanism by which age-associated loss of specialized actin networks impacts tissue integrity.

Original languageEnglish (US)
Pages (from-to)587-601.e7
JournalDevelopmental cell
Issue number5
StatePublished - Dec 2 2019


  • HSF-1
  • actin
  • aging
  • barrier
  • intestine
  • junctions
  • kinase
  • pathogenesis
  • phosphorylation
  • stress

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology


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