Regulation of epithelial integrity and organ growth by Tctp and Coracle in Drosophila

PLoS Genet. 2020 Jun 19;16(6):e1008885. doi: 10.1371/journal.pgen.1008885. eCollection 2020 Jun.

Abstract

Regulation of cell junctions is crucial for the integrity of epithelial tissues and organs. Cell junctions also play roles in controlling cell proliferation for organ growth. Translationally controlled tumor protein (TCTP) is a conserved protein involved in growth control, but its role in cell junctions is unknown. Here we show that Drosophila Tctp directly interacts with the septate junction protein Coracle (Cora) to regulate epithelial integrity and organ growth. Tctp localizes together with Cora in the epidermis of the embryo. Loss of Cora reduces the level of Tctp in the epidermis but not vice versa. cora/+ or Tctp/+ single heterozygotes develop normally to adulthood. However, double heterozygotes for cora and Tctp mutations show severe disruption of epithelia causing synthetic lethality in the embryo. Double knockdown of Cora and Tctp in eye imaginal disc synergistically leads to disruption of the eye disc, resulting in a severe reduction or loss of eye and head. Conversely, double knockdown of Cora and Tctp in wing disc causes overgrowth as well as cell death. Inhibition of cell death under this condition causes hyperplastic growth of the wing disc. Tctp also shows direct and functional interaction with Cora-associated factors like Yurt and Na+/K+-ATPase. This study suggests that proper levels of Tctp and Cora are essential for the maintenance of the Cora complex and the integrity of epithelia. Our data also provide evidence that both Cora and Tctp are required to suppress overgrowth in developing wing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation / genetics
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / physiology*
  • Embryo, Nonmammalian
  • Epithelium / metabolism*
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Imaginal Discs / growth & development
  • Intercellular Junctions / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Morphogenesis / genetics
  • Synthetic Lethal Mutations
  • Wings, Animal / growth & development*
  • Wings, Animal / metabolism

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • TCTP protein, Drosophila
  • cora protein, Drosophila
  • yrt protein, Drosophila

Grants and funding

This research was supported by grants (NRF-2014K1A1A2042982 and NRF-2017R1A2B3007516 to K.-W.C, NRF-35B-2011-1-C00033 and NRF-2016 R1D1A1B03932039 to S.-T.H) of the National Research Foundation of Korea funded by the Ministry of Education, Science & Technology, Republic of Korea (http://www.nrf.re.kr/eng/index). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.