A functional coupling between CRMP1 and Na(v)1.7 for retrograde propagation of Semaphorin3A signaling

作者：Yamane Masayuki; Yamashita Naoya^*; Hida Tomonobu; Kamiya Yoshinori; Nakamura Fumio; Kolattukudy Pappachan; Goshima Yoshio^*

来源：Journal of Cell Science, 2017, 130(8): 1393-1403.

DOI：10.1242/jcs.199737

• Semaphorin3A
• CRMP1
• Voltage
• dependent Na+ channels
• TrkA
• PlexA4
• Axonal transport

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 Na(v)1.7 (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 Na(v)1.7 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 Na(v)1.7 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 Na(v)1.7. These results suggest that Na(v)1.7, by coupling with CRMP1, mediates the axonal retrograde signaling of Sema3A.

• 出版日期2017-4-15
• 单位RIKEN