A functional coupling between CRMP1 and Nav1.7 for retrograde propagation of Semaphorin3A signaling.
J Cell Sci
; 130(8): 1393-1403, 2017 04 15.
Article
en En
| MEDLINE
| ID: mdl-28254884
ABSTRACT
Semaphorin3A (Sema3A) is a secreted type of axon guidance molecule that regulates axon wiring through complexes of neuropilin-1 (NRP1) with PlexinA protein receptors. Sema3A regulates the dendritic branching through tetrodotoxin (TTX)-sensitive retrograde axonal transport of PlexA proteins and tropomyosin-related kinase A (TrkA) complex. We here demonstrate that Nav1.7 (encoded by SCN9A), a TTX-sensitive Na+ channel, by coupling with collapsin response mediator protein 1 (CRMP1), mediates the Sema3A-induced retrograde transport. In mouse dorsal root ganglion (DRG) neurons, Sema3A increased co-localization of PlexA4 and TrkA in the growth cones and axons. TTX treatment and RNAi knockdown of Nav1.7 sustained Sema3A-induced colocalized signals of PlexA4 and TrkA in growth cones and suppressed the subsequent localization of PlexA4 and TrkA in distal axons. A similar localization phenotype was observed in crmp1-/- DRG neurons. Sema3A induced colocalization of CRMP1 and Nav1.7 in the growth cones. The half maximal voltage was increased in crmp1-/- neurons when compared to that in wild type. In HEK293 cells, introduction of CRMP1 lowered the threshold of co-expressed exogenous Nav1.7. These results suggest that Nav1.7, by coupling with CRMP1, mediates the axonal retrograde signaling of Sema3A.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Semaforina-3A
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Canal de Sodio Activado por Voltaje NAV1.7
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Orientación del Axón
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Ganglios Espinales
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Proteínas del Tejido Nervioso
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Neuronas
Tipo de estudio:
Guideline
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Sci
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón