The exocyst functions in niche cells to promote germline stem cell differentiation by directly controlling EGFR membrane trafficking

Development. 2019 Jun 28;146(13):dev174615. doi: 10.1242/dev.174615.

Abstract

The niche controls stem cell self-renewal and differentiation in animal tissues. Although the exocyst is known to be important for protein membrane trafficking and secretion, its role in stem cells and niches has never been reported. Here, this study shows that the exocyst functions in the niche to promote germline stem cell (GSC) progeny differentiation in the Drosophila ovary by directly regulating EGFR membrane trafficking and signaling. Inactivation of exocyst components in inner germarial sheath cells, which form the differentiation niche, causes a severe GSC differentiation defect. The exocyst is required for maintaining niche cells and preventing BMP signaling in GSC progeny by promoting EGFR membrane targeting and signaling through direct association with EGFR. Finally, it is also required for EGFR membrane targeting, recycling and signaling in human cells. Therefore, this study reveals a novel function of the exocyst in niche cells to promote stem cell progeny differentiation by directly controlling EGFR membrane trafficking and signaling in vivo, and also provides important insight into how the niche controls stem cell progeny differentiation at the molecular level.

Keywords: Differentiation; Drosophila; EGFR; Exocyst; GSC; Human; Niche; Stem cell.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation* / genetics
  • Cell Membrane / metabolism
  • Cell Self Renewal / genetics
  • Cells, Cultured
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • ErbB Receptors / metabolism*
  • ErbB Receptors / physiology
  • Female
  • GTP-Binding Proteins / physiology
  • Germ Cells / cytology*
  • Germ Cells / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / physiology
  • Ovary / cytology
  • Ovary / metabolism
  • Protein Transport / genetics
  • Receptors, Invertebrate Peptide / metabolism*
  • Receptors, Invertebrate Peptide / physiology
  • Stem Cell Niche* / genetics
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / physiology*

Substances

  • Drosophila Proteins
  • EXOC5 protein, human
  • EXOC6B protein, human
  • Multiprotein Complexes
  • Receptors, Invertebrate Peptide
  • Vesicular Transport Proteins
  • Egfr protein, Drosophila
  • ErbB Receptors
  • GTP-Binding Proteins