The Role of pkc-3 and Genetic Suppressors in Caenorhabditis elegans Epithelial Cell Junction Formation

Genetics. 2020 Apr;214(4):941-959. doi: 10.1534/genetics.120.303085. Epub 2020 Jan 31.


Epithelial cells form intercellular junctions to strengthen cell-cell adhesion and limit diffusion, allowing epithelia to function as dynamic tissues and barriers separating internal and external environments. Junctions form as epithelial cells differentiate; clusters of junction proteins first concentrate apically, then mature into continuous junctional belts that encircle and connect each cell. In mammals and Drosophila, atypical protein kinase C (aPKC) is required for junction maturation, although how it contributes to this process is poorly understood. A role for the Caenorhabditis elegans aPKC homolog PKC-3 in junction formation has not been described previously. Here, we show that PKC-3 is essential for junction maturation as epithelia first differentiate. Using a temperature-sensitive allele of pkc-3 that causes junction breaks in the spermatheca and leads to sterility, we identify intragenic and extragenic suppressors that render pkc-3 mutants fertile. Intragenic suppressors include an unanticipated stop-to-stop mutation in the pkc-3 gene, providing evidence for the importance of stop codon identity in gene activity. One extragenic pkc-3 suppressor is a loss-of-function allele of the lethal(2) giant larvae homolog lgl-1, which antagonizes aPKC within epithelia of Drosophila and mammals, but was not known previously to function in C. elegans epithelia. Finally, two extragenic suppressors are loss-of-function alleles of sups-1-a previously uncharacterized gene. We show that SUPS-1 is an apical extracellular matrix protein expressed in epidermal cells, suggesting that it nonautonomously regulates junction formation in the spermatheca. These findings establish a foundation for dissecting the role of PKC-3 and interacting genes in epithelial junction maturation.

Keywords: aPKC; adherens junction; cell polarity; kinase; stop codon; suppressor.

Publication types

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

MeSH terms

  • Adherens Junctions / metabolism*
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Polarity
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Mutation
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Suppression, Genetic*


  • Caenorhabditis elegans Proteins
  • LGL-1 protein, C elegans
  • PKC-3 protein
  • Protein Kinase C