PT  - JOURNAL ARTICLE
AU  - Wallace, Andre G.
AU  - Raduwan, Hamidah
AU  - Carlet, John
AU  - Soto, Martha C.
TI  - The RhoGAP myosin 9/HUM-7 integrates membrane signals to modulate Rho/RHO-1 during embryonic morphogenesis in <em>C. elegans</em>
AID  - 10.1101/325274
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 325274
4099  - http://biorxiv.org/content/early/2018/05/17/325274.short
4100  - http://biorxiv.org/content/early/2018/05/17/325274.full
AB  - During embryonic morphogenesis, cells and tissues undergo dramatic movements under the control of F-actin regulators. Our studies of epidermal cell migrations in developing C. elegans embryos have identified multiple plasma membrane signals that regulate the Rac GTPase, thus regulating WAVE and Arp2/3 complexes, to promote branched F-actin formation and polarized enrichment. We describe here a pathway that acts in parallel to Rac to transduce membrane signals to control epidermal F-actin through the GTPase Rho. Rho contributes to epidermal migrations through effects on underlying neuroblasts. Here we identify signals to regulate Rho in the epidermis. HUM-7, the C. elegans homolog of human Myo9A and Myo9B, regulates F-actin dynamics during epidermal migrations, by controlling Rho. Genetics and biochemistry support that HUM-7 behaves as GAP for the Rho GTPase, so that loss of HUM-7 enhances Rho-dependent epidermal cell behaviors. We identify SAX-3/ROBO as an upstream signal that contributes to attenuated Rho activation through its regulation of HUM-7/Myo9. These studies identify a new role for Rho during epidermal cell migrations, and suggest that Rho activity is regulated by SAX-3/ROBO acting on the RhoGAP HUM-7.