SNX482 inhibits semaphorin 3A induced sensory axon growth cone collapse

Abstract

During axon navigation and regeneration after injuries a guidance molecule semaphorin 3A (sema3A) is one of the principalproteins in repulsing axons and inhibiting their growth. It is nowknown that calcium (Ca2+) is important in axon response toattractive guidance cues. On the other hand it still remains elusive if this is also true for repulsive guidance cue sema3A. In thisstudy intracellular calcium ([Ca2 + ]i) imaging was used to evaluate if sema3A-induced growth cone collapse is Ca2+dependent.[Ca2+]iimaging with ratiometric dye Fura-2 AM showed Ca2+increase in E15 mice dorsal root ganglia neuron growth cones inresponse to sema3A. Therefore Sema3A effects on growth conesafter modifying [Ca2+]iand [Ca2+]echannels that we have shownare expressed in E15 mouse embryos were evaluated. Results ofour study showed that sema3A indeed increased growth cone collapse rate that was blocked by the non-selective R- and T- typeCa2+channel inhibitor NiCl2and by the selective R-type Ca2+channel inhibitor SNX482. Ca2+channel inhibitors used havedecreased the sema3A-induced [Ca2+]iconcentration elevation. Results of this study demonstrated that sema3A-induced growth cone collapses are related to the increase in [Ca2+]iconcentrationin sensory axon growth cones and this is mediated through the R-type calcium channels.