Changes in endolysosomal organization define a pre-degenerative state in the crumbs mutant Drosophila retina

PLoS One. 2019 Dec 13;14(12):e0220220. doi: 10.1371/journal.pone.0220220. eCollection 2019.

Abstract

Mutations in the epithelial polarity gene crumbs (crb) lead to retinal degeneration in Drosophila and in humans. The overall morphology of the retina and its deterioration in Drosophila crb mutants has been well-characterized, but the cell biological origin of the degeneration is not well understood. Degenerative conditions in the retina and elsewhere in the nervous system often involve defects in degradative intracellular trafficking pathways. So far, however, effects of crb on the endolysosomal system, or on the spatial organization of these compartments in photoreceptor cells have not been described. We therefore asked whether photoreceptors in crb mutants exhibit alterations in endolysosomal compartments under pre-degenerative conditions, where the retina is still morphologically intact. Data presented here show that, already well before the onset of degeneration, Arl8, Rab7, and Atg8-carrying endolysosomal and autophagosomal compartments undergo changes in morphology and positioning with respect to each other in crb mutant retinas. We propose that these changes may be early signs of the degeneration-prone condition in crb retinas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism
  • Animals
  • Cell Polarity / genetics
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Endosomes / metabolism
  • Eye Proteins / genetics
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Photoreceptor Cells, Invertebrate / metabolism
  • Protein Transport / genetics
  • Retina / metabolism
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / prevention & control
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism
  • rab7 GTP-Binding Proteins

Substances

  • Arl8 protein, Drosophila
  • Drosophila Proteins
  • Eye Proteins
  • Membrane Proteins
  • crb protein, Drosophila
  • rab7 GTP-Binding Proteins
  • rab7 GTP-binding proteins, human
  • ADP-Ribosylation Factors
  • rab GTP-Binding Proteins

Grants and funding

This work was supported by the Max-Planck Society (https://www.mpg.de/en). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.