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

doi:10.1371/journal.pone.0113428

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

PLoS One. 2014 Nov 19;9(11):e113428. doi: 10.1371/journal.pone.0113428. eCollection 2014.

Authors

Anastasia Abashidze¹, Veronica Gold¹, Yaron Anavi², Hayit Greenspan³, Miguel Weil¹

Affiliations

¹ Laboratory for Neurodegenerative Diseases and Personalized Medicine, Department of Cell Research and Immunology, The Sagol School of Neurosciences, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
² Department of Applied Mathematics, School of Mathematical Sciences, Tel Aviv University, Tel Aviv, Israel.
³ Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axons / metabolism
Carrier Proteins / antagonists & inhibitors
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Movement
Cells, Cultured
Chick Embryo
Chickens
Dyneins / metabolism
Dysautonomia, Familial / genetics
Dysautonomia, Familial / pathology
Ganglia, Spinal / cytology
JNK Mitogen-Activated Protein Kinases / metabolism*
Microscopy, Fluorescence
Nerve Growth Factor / metabolism*
Neurons / cytology
Neurons / metabolism
Peripheral Nervous System / growth & development
Peripheral Nervous System / pathology*
RNA Interference
RNA, Small Interfering / metabolism
Signal Transduction
Tubulin / chemistry
Tubulin / metabolism

Substances

Carrier Proteins
RNA, Small Interfering
Tubulin
Nerve Growth Factor
JNK Mitogen-Activated Protein Kinases
Dyneins

Grants and funding

This study was supported by the FD research consortium (FD Hope, FD Foundation Inc., FD Israel Foundation) and by the Israel Science Foundation (ISF grant 1491/09). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.