A functional coupling between CRMP1 and Nav1.7 for retrograde propagation of Semaphorin3A signaling

• Published in: Journal of cell science Vol. 130; no. 8; pp. 1393 - 1403
• Main Authors: Yamane, Masayuki, Yamashita, Naoya, Hida, Tomonobu, Kamiya, Yoshinori, Nakamura, Fumio, Kolattukudy, Pappachan, Goshima, Yoshio
• Format: Journal Article
• Language: English
• Published: Cambridge The Company of Biologists Ltd 15.04.2017
• Subjects: Axon guidance; Axonal transport; Axonogenesis; Axons; Cell body; Coding; Cones; Coupling; Dendritic branching; Dorsal root ganglia; Growth cones; Localization; Mediator protein; Neurons; Neuropilin; Proteins; Receptors; Retrograde transport; RNA-mediated interference; Semaphorins; Signaling; Sodium channels (voltage-gated); Tetrodotoxin; Transport; TrkA protein; TrkA receptors; Tropomyosin; Wiring
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.199737

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.