C. elegans RAP-1 reinforces LET-60/Ras induction of cell fate Institutional Repository Document uri icon


  • AbstractThe notoriety of the small GTPase Ras as the most mutated oncoprotein has led to a well-characterized signaling network largely conserved across metazoans. Yet the role of its close relative Rap1 (Ras Proximal), which shares 100% identity between their core effector binding sequences, remains unclear. A long-standing controversy in the field is whether Rap1 also functions to activate the canonical Ras effector, the S/T kinase Raf. We used the developmentally simplerCaenorhabditis elegans, which lacks the extensive paralog redundancy of vertebrates, to examine the role of RAP-1 in two distinct LET-60/Ras-dependent cell fate patterning events: induction of 1 vulval precursor cell (VPC) fate and of the excretory duct cell. Fluorescently tagged endogenous RAP-1 is localized to plasma membranes and is expressed ubiquitously, with even expression levels across the VPCs. RAP-1 and its activating GEF PXF-1 function cell autonomously and are necessary for maximal induction of 1 VPCs. Critically, mutationally activated endogenous RAP-1 is sufficient both to induce ectopic 1s and duplicate excretory duct cells. Like endogenous RAP-1, before induction GFP expression from thepxf-1promoter is uniform across VPCs. However, unlike endogenous RAP-1, after induction GFP expression is increased in presumptive 1s and decreased in presumptive 2s. We conclude that RAP-1 is a positive regulator that promotes Ras-dependent inductive fate decisions. We hypothesize that PXF-1 activation of RAP-1 serves as a minor parallel input into the major LET-60/Ras signal through LIN-45/Raf.

altmetric score

  • 8.934

author list (cited authors)

  • Rasmussen, N. R., Dickinson, D. J., & Reiner, D. J.

citation count

  • 0

complete list of authors

  • Rasmussen, Neal R||Dickinson, Daniel J||Reiner, David J

Book Title

  • bioRxiv

publication date

  • April 2018