The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis

Stem Cell Reports. 2019 May 14;12(5):1024-1040. doi: 10.1016/j.stemcr.2019.03.008. Epub 2019 Apr 18.

Abstract

Tissue homeostasis and repair relies on proper communication of stem cells and their differentiating daughters with the local tissue microenvironment. In the Drosophila male germline adult stem cell lineage, germ cells proliferate and progressively differentiate enclosed in supportive somatic cyst cells, forming a small organoid, the functional unit of differentiation. Here we show that cell polarity and vesicle trafficking influence signal transduction in cyst cells, with profound effects on the germ cells they enclose. Our data suggest that the cortical components Dlg, Scrib, Lgl and the clathrin-mediated endocytic (CME) machinery downregulate epidermal growth factor receptor (EGFR) signaling. Knockdown of dlg, scrib, lgl, or CME components in cyst cells resulted in germ cell death, similar to increased signal transduction via the EGFR, while lowering EGFR or downstream signaling components rescued the defects. This work provides insights into how cell polarity and endocytosis cooperate to regulate signal transduction and sculpt developing tissues.

Keywords: Drosophila spermatogenesis; EGFR regulation; PIP(2); clathrin; dlg; endocytosis; lgl; polarity; scrib; septate junctions.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Polarity / genetics
  • Clathrin / metabolism*
  • Cysts / genetics
  • Cysts / metabolism*
  • Cysts / pathology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Endocytosis / genetics
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Germ Cells / cytology
  • Germ Cells / metabolism*
  • Male
  • RNA Interference
  • Signal Transduction / genetics
  • Spermatogenesis / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Testis / cytology
  • Testis / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Clathrin
  • Drosophila Proteins
  • Tumor Suppressor Proteins
  • dlg1 protein, Drosophila
  • ErbB Receptors