p190RhoGAP Filters Competing Signals to Resolve Axon Guidance Conflicts.
Neuron
; 102(3): 602-620.e9, 2019 05 08.
Article
en En
| MEDLINE
| ID: mdl-30902550
ABSTRACT
The rich functional diversity of the nervous system is founded in the specific connectivity of the underlying neural circuitry. Neurons are often preprogrammed to respond to multiple axon guidance signals because they use sequential guideposts along their pathways, but this necessitates a strict spatiotemporal regulation of intracellular signaling to ensure the cues are detected in the correct order. We performed a mouse mutagenesis screen and identified the Rho GTPase antagonist p190RhoGAP as a critical regulator of motor axon guidance. Rather than acting as a compulsory signal relay, p190RhoGAP uses a non-conventional GAP-independent mode to transiently suppress attraction to Netrin-1 while motor axons exit the spinal cord. Once in the periphery, a subset of axons requires p190RhoGAP-mediated inhibition of Rho signaling to target specific muscles. Thus, the multifunctional activity of p190RhoGAP emerges from its modular design. Our findings reveal a cell-intrinsic gate that filters conflicting signals, establishing temporal windows of signal detection.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Músculo Esquelético
/
Proteínas Activadoras de GTPasa
/
Orientación del Axón
/
Netrina-1
/
Receptor DCC
/
Neuronas Motoras
Tipo de estudio:
Guideline
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2019
Tipo del documento:
Article