Polarized secretion of Drosophila EGFR ligand from photoreceptor neurons is controlled by ER localization of the ligand-processing machinery

PLoS Biol. 2010 Oct 5;8(10):e1000505. doi: 10.1371/journal.pbio.1000505.

Abstract

The release of signaling molecules from neurons must be regulated, to accommodate their highly polarized structure. In the developing Drosophila visual system, photoreceptor neurons secrete the epidermal growth factor receptor ligand Spitz (Spi) from their cell bodies, as well as from their axonal termini. Here we show that subcellular localization of Rhomboid proteases, which process Spi, determines the site of Spi release from neurons. Endoplasmic reticulum (ER) localization of Rhomboid 3 is essential for its ability to promote Spi secretion from axons, but not from cell bodies. We demonstrate that the ER extends throughout photoreceptor axons, and show that this feature facilitates the trafficking of the Spi precursor, the ligand chaperone Star, and Rhomboid 3 to axonal termini. Following this trafficking step, secretion from the axons is regulated in a manner similar to secretion from cell bodies. These findings uncover a role for the ER in trafficking proteins from the neuronal cell body to axon terminus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Polarity*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster* / cytology
  • Drosophila melanogaster* / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / ultrastructure
  • Endosomes / metabolism
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / metabolism*
  • Ligands*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Photoreceptor Cells, Invertebrate / metabolism*
  • Photoreceptor Cells, Invertebrate / ultrastructure*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology

Substances

  • Drosophila Proteins
  • Ligands
  • Membrane Proteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Rho protein, Drosophila
  • spi protein, Drosophila
  • Epidermal Growth Factor
  • ErbB Receptors