Activity of all JNK isoforms contributes to neurite growth in spiral ganglion neurons

Patrick J Atkinson; Chang-Hyun Cho; Marlan R Hansen; Steven H Green

doi:10.1016/j.heares.2011.04.011

Back

Activity of all JNK isoforms contributes to neurite growth in spiral ganglion neurons

Journal article

Peer reviewed

Activity of all JNK isoforms contributes to neurite growth in spiral ganglion neurons

Patrick J Atkinson, Chang-Hyun Cho, Marlan R Hansen and Steven H Green

Hearing research, Vol.278(1-2), pp.77-85

08/2011

DOI: 10.1016/j.heares.2011.04.011

PMCID: PMC3152600

PMID: 21554942

View Online

Abstract

Jun N-terminal kinase (JNK) is a multifunctional protein kinase crucial for neuronal apoptosis as well as neurite growth. We have previously shown that JNK activity is correlated with spiral ganglion neuron (SGN) apoptosis following hair cell loss in rats (Alam et al., 2007) implying that JNK inhibition may have therapeutic potential to protect SGNs in deaf individuals. Here we investigated the role of JNK in neurite outgrowth from cultured neonatal rat and mouse SGNs. We show that JNK is required for initial growth of neurites and for continued extension of already established neurites. The effect of JNK inhibition on neurite growth is rapid and is also rapidly reversible after washout of the inhibitor. Using phosphoJNK immunoreactivity as an indicator, we show that JNK is activated in growth cones within 30 min after transfer to medium lacking neurotrophic stimuli (5 K medium) but activation in the nucleus and soma requires hours. By transfecting epitope-tagged JNK1, JNK2, or JNK3 isoforms into SGNs, we found that all are present in the nucleus and cytoplasm and that there is no preferential redistribution to the nucleus after transfer to 5 K medium. Cotransfection of dominant-negative (dn) JNK1 and JNK2 into SGNs reduced neurite growth, although transfection of dnJNK1 or dnJNK2 alone had no significant effect. SGNs cultured from JNK3(-/-) mice showed reduced neurite growth that was further reduced by transfection of dnJNK1 and dnJNK2. This indicates that all three JNK isoforms promote SGN neurite growth although there may be functional redundancy between JNK1 and JNK2.

Spiral Ganglion - enzymology

Phosphorylation

Spiral Ganglion - ultrastructure

Neurites - enzymology

Mitogen-Activated Protein Kinase 9 - genetics

Mitogen-Activated Protein Kinase 10 - genetics

MAP Kinase Signaling System

Neurons - ultrastructure

Transfection

Neurites - ultrastructure

Mitogen-Activated Protein Kinase 8 - genetics

Mitogen-Activated Protein Kinase 9 - metabolism

Mitogen-Activated Protein Kinase 8 - metabolism

Cells, Cultured

Rats

MAP Kinase Kinase Kinases - metabolism

Spiral Ganglion - innervation

Mitogen-Activated Protein Kinase 9 - deficiency

Mice, Knockout

Mitogen-Activated Protein Kinase 10 - metabolism

Mitogen-Activated Protein Kinase 8 - deficiency

Animals

Neurons - enzymology

Mice

Mitogen-Activated Protein Kinase 10 - deficiency

Enzyme Activation

Kinetics

Subcellular Fractions - enzymology

Details

Title: Subtitle: Activity of all JNK isoforms contributes to neurite growth in spiral ganglion neurons
Creators: Patrick J Atkinson - Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242, USA
Chang-Hyun Cho
Marlan R Hansen
Steven H Green
Resource Type: Journal article
Publication Details: Hearing research, Vol.278(1-2), pp.77-85
DOI: 10.1016/j.heares.2011.04.011
PMID: 21554942
PMCID: PMC3152600
NLM abbreviation: Hear Res
ISSN: 0378-5955
eISSN: 1878-5891
Publisher: Netherlands
Grant note: R01 DC002961-15 / NIDCD NIH HHS R01 DC009801 / NIDCD NIH HHS K08 DC006211 / NIDCD NIH HHS P30 DC010362 / NIDCD NIH HHS R01 DC002961 / NIDCD NIH HHS P30 DC010362-02 / NIDCD NIH HHS R01 DC02961 / NIDCD NIH HHS KO8 DC006211-01A1 / NIDCD NIH HHS R01 DC009405 / NIDCD NIH HHS
Language: English
Date published: 08/2011
Academic Unit: Molecular Physiology and Biophysics; Biology; Neurosurgery; Otolaryngology
Record Identifier: 9984006334502771

Metrics

25 Record Views

24 Times Cited - Web of Science