The small GTPase Rap1 is a modulator of Hedgehog signaling.
During development, the evolutionarily conserved Hedgehog (Hh) morphogen provides instructional cues that influence cell fate, cell affinity and tissue morphogenesis. To do so, the Hh signaling cascade must coordinate its activity with other morphogenetic signals. This can occur through engagement of or response to effectors that do not typically function as core Hh pathway components. Given the ability of small G proteins of the Ras family to impact cell survival, differentiation, growth and adhesion, we wanted to determine whether Hh and Ras signaling might intersect during development. We performed genetic modifier tests in Drosophila to examine the ability of select Ras family members to influence Hh signal output, and identified Rap1 as a positive modulator of Hh pathway activity. Our results suggest that Rap1 is activated to its GTP-bound form in response to Hh ligand, and that the GTPase exchange factor C3G likely contributes to this activation. The Rap1 effector Canoe (Cno) also impacts Hh signal output, suggesting that a C3G-Rap1-Cno axis intersects the Hh pathway during tissue morphogenesis.
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, United States.
Suresh
S
Marada
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, United States; Rhodes College Summer Plus Program, Rhodes College, Memphis, TN 38112, United States.
Ashley
A
Truong
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, United States. Electronic address: Stacey.Ogden@stjude.org.
Stacey K
SK
Ogden
D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D016153:Genes, Suppressor; D006160:Guanosine Triphosphate / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D000089804:Shelterin Complex; D015398:Signal Transduction; D034501:Telomere-Binding Proteins / Q000378:metabolism*
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; C000607855:RAP1 protein, Drosophila; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C092747:cno protein, Drosophila; C077245:hh protein, Drosophila; D006160:Guanosine Triphosphate
GTPase; Hedgehog; Morphogenesis; Rap1; Signal transduction