A Functional Coupling Between Crmp1 And NaV1.7 For Retrograde Propagation Of Semaphorin3A Signaling

Keywords

Axonal transport; CRMP1; PlexA4; Semaphorin3A; TrkA; Voltage-dependent Na channels +

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 Sema3Ainduced 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 CRMP1lowered 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.

Publication Date

4-15-2017

Publication Title

Journal of Cell Science

Volume

130

Issue

8

Number of Pages

1393-1403

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1242/jcs.199737

Socpus ID

85017567081 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85017567081

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