Apical accumulation of the Sevenless receptor tyrosine kinase during Drosophila eye development is promoted by the small GTPase Rap1

Genetics. 2014 Aug;197(4):1237-50. doi: 10.1534/genetics.114.166272. Epub 2014 Jun 3.

Abstract

The Ras/MAPK-signaling pathway plays pivotal roles during development of metazoans by controlling cell proliferation and cell differentiation elicited, in several instances, by receptor tyrosine kinases (RTKs). While the internal mechanism of RTK-driven Ras/MAPK signaling is well understood, far less is known regarding its interplay with other co-required signaling events involved in developmental decisions. In a genetic screen designed to identify new regulators of RTK/Ras/MAPK signaling during Drosophila eye development, we identified the small GTPase Rap1, PDZ-GEF, and Canoe as components contributing to Ras/MAPK-mediated R7 cell differentiation. Rap1 signaling has recently been found to participate in assembling cadherin-based adherens junctions in various fly epithelial tissues. Here, we show that Rap1 activity is required for the integrity of the apical domains of developing photoreceptor cells and that reduced Rap1 signaling hampers the apical accumulation of the Sevenless RTK in presumptive R7 cells. It thus appears that, in addition to its role in cell-cell adhesion, Rap1 signaling controls the partitioning of the epithelial cell membrane, which in turn influences signaling events that rely on apico-basal cell polarity.

Keywords: Drosophila eye development; MAPK; Rap1; Ras; receptor tyrosine kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adherens Junctions / genetics
  • Adherens Junctions / metabolism
  • Animals
  • Cell Adhesion / genetics
  • Cell Differentiation / genetics
  • Cell Polarity / genetics
  • Chromosome Mapping
  • Drosophila / embryology
  • Drosophila / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Epithelial Cells / metabolism
  • Eye / embryology*
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • MAP Kinase Signaling System
  • Organogenesis / genetics
  • Photoreceptor Cells, Invertebrate / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • rap1 GTP-Binding Proteins / genetics
  • rap1 GTP-Binding Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • CNK protein, Drosophila
  • Drosophila Proteins
  • Eye Proteins
  • Receptor Protein-Tyrosine Kinases
  • sev protein, Drosophila
  • rap1 GTP-Binding Proteins