Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons

Anastasia Abashidze, Veronica Gold, Yaron Anavi, Hayit Greenspan, Miguel Weil

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKAP is required for proper axonal outgrowth, branching, and peripheral target innervation. Moreover, we demonstrate that IKAP colocalizes with activated JNK (pJNK), dynein, and β-tubulin at the axon terminals of dorsal root ganglia (DRG) neurons, and may be involved in transport of specific target derived signals required for transcription of JNK and NGF responsive genes in the nucleus. These results suggest the novel role of IKAP in neuronal transport and specific signaling mediated transcription, and provide, for the first time, the basis for a molecular mechanism behind the FD phenotype.

Original languageEnglish
Article numbere113428
JournalPLoS ONE
Volume9
Issue number11
DOIs
StatePublished - 19 Nov 2014

Funding

FundersFunder number
Israel Science Foundation1491/09

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