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Development ; 145(23)2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30389847

RESUMO

During embryonic morphogenesis, cells and tissues undergo dramatic movements under the control of F-actin regulators. Our studies of epidermal cell migrations in developing Caenorhabditiselegans 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. Here, we describe a pathway that acts in parallel to Rac to transduce membrane signals to control epidermal F-actin through the GTPase RHO-1/RhoA. RHO-1 contributes to epidermal migration through effects on underlying neuroblasts. We identify signals to regulate RHO-1-dependent events in the epidermis. HUM-7, the C. elegans homolog of human MYO9A and MYO9B, regulates F-actin dynamics during epidermal migration. Genetics and biochemistry support that HUM-7 behaves as a GTPase-activating protein (GAP) for the RHO-1/RhoA and CDC-42 GTPases. Loss of HUM-7 enhances RHO-1-dependent epidermal cell behaviors. We identify SAX-3/ROBO as an upstream signal that contributes to attenuated RHO-1 activation through its regulation of HUM-7/Myo9. These studies identify a new role for RHO-1 during epidermal cell migration, and suggest that RHO-1 activity is regulated by SAX-3/ROBO acting on the RhoGAP HUM-7.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/metabolismo , Embrião não Mamífero/metabolismo , Morfogênese , Proteínas rho de Ligação ao GTP/metabolismo , Actinas/metabolismo , Animais , Orientação de Axônios , Caenorhabditis elegans/citologia , Proteínas de Ciclo Celular/metabolismo , Movimento Celular , Embrião não Mamífero/citologia , Epiderme/metabolismo , Epistasia Genética , Proteínas de Ligação ao GTP/metabolismo , Larva/metabolismo , Músculos/metabolismo , Fenótipo
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