PT  - JOURNAL ARTICLE
AU  - Jordan T. Silver
AU  - Frederik Wirtz-Peitz
AU  - Sérgio Simões
AU  - Milena Pellikka
AU  - Dong Yan
AU  - Richard Binari
AU  - Takashi Nishimura
AU  - Yan Li
AU  - Tony J. C. Harris
AU  - Norbert Perrimon
AU  - Ulrich Tepass
TI  - The RhoGEF Cysts couples apical polarity proteins to Rho and myosin activity at adherens junctions
AID  - 10.1101/617134
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 617134
4099  - http://biorxiv.org/content/early/2019/04/24/617134.short
4100  - http://biorxiv.org/content/early/2019/04/24/617134.full
AB  - The spatio-temporal regulation of small Rho GTPases is crucial for the dynamic stability of epithelial tissues. However, how RhoGTPase activity is controlled during development remains largely unknown. To explore the regulation of Rho GTPases in vivo we analyzed the Rho GTPase guanine nucleotide exchange factor (RhoGEF) Cysts, the Drosophila orthologue of mammalian p114RhoGEF, GEF-H1, p190RhoGEF, and AKAP-13. Loss of Cysts causes a phenotype that closely resemble the mutant phenotype of the apical polarity regulator Crumbs. This phenotype can be suppressed by the loss of basolateral polarity proteins suggesting that Cysts in an integral component of the apical polarity protein network. Cysts activates Rho at adherens junctions to promote junctional enrichment of myosin II, which requires the RhoGEF domain and the coiled-coil domain containing C-terminal region of Cysts. Cysts recruitment to the apico-lateral cortex depends on Crumbs and Bazooka/Par3 and requires multiple domains within Cysts including the C-terminal region. Together, our findings indicate that Cysts links apical polarity proteins to Rho1 and myosin activation at adherens junctions to support junctional and epithelial integrity in the Drosophila ectoderm.