CaMKII and CaMKIV mediate distinct prosurvival signaling pathways in response to depolarization in neurons

Jinwoong Bok; Qiong Wang; Jie Huang; Steven H Green

doi:10.1016/j.mcn.2007.05.008

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CaMKII and CaMKIV mediate distinct prosurvival signaling pathways in response to depolarization in neurons

Journal article

Peer reviewed

CaMKII and CaMKIV mediate distinct prosurvival signaling pathways in response to depolarization in neurons

Jinwoong Bok, Qiong Wang, Jie Huang and Steven H Green

Molecular and cellular neurosciences, Vol.36(1), pp.13-26

09/2007

DOI: 10.1016/j.mcn.2007.05.008

PMCID: PMC2040167

PMID: 17651987

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Abstract

By fusing the CaMKII-inhibitory peptide AIP to GFP, we constructed a specific and effective CaMKII inhibitor, GFP-AIP. Expression of GFP-AIP and/or dominant-inhibitory CaMKIV in cultured neonatal rat spiral ganglion neurons (SGNs) shows that CaMKII and CaMKIV act additively and in parallel to mediate the prosurvival effect of depolarization. Depolarization or expression of constitutively active CaMKII functionally inactivates Bad, indicating that this is one means by which CaMKII promotes neuronal survival. CaMKIV, but not CaMKII, requires CREB to promote SGN survival, consistent with the exclusively nuclear localization of CaMKIV and indicating that the principal prosurvival function of CaMKIV is activation of CREB. Consistent with this, a constitutively active CREB construct that provides a high level of CREB activity promotes SGN survival, although low levels of CREB activity did not do so. Also, in apoptotic SGNs, activation of CREB by depolarization is disabled, presumably as part of a cellular commitment to apoptosis.

Transfection

Animals

Animals, Newborn

bcl-Associated Death Protein - metabolism

Calcium-Calmodulin-Dependent Protein Kinase Type 2 - physiology

Calcium-Calmodulin-Dependent Protein Kinase Type 4 - physiology

Cell Nucleus - drug effects

Cell Nucleus - metabolism

Cell Survival - genetics

Cell Survival - physiology

CREB-Binding Protein - metabolism

Dose-Response Relationship, Drug

Enzyme Activation - genetics

Enzyme Activation - physiology

Gene Expression Regulation - drug effects

Green Fluorescent Proteins - metabolism

Neurofilament Proteins - metabolism

Neurons - drug effects

Neurons - physiology

Neurons - ultrastructure

Peptides - metabolism

Potassium Chloride - pharmacology

Rats

Signal Transduction - physiology

Spiral Ganglion - cytology

Details

Title: Subtitle: CaMKII and CaMKIV mediate distinct prosurvival signaling pathways in response to depolarization in neurons
Creators: Jinwoong Bok - Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, USA
Qiong Wang
Jie Huang - University of Iowa
Steven H Green
Resource Type: Journal article
Publication Details: Molecular and cellular neurosciences, Vol.36(1), pp.13-26
DOI: 10.1016/j.mcn.2007.05.008
PMID: 17651987
PMCID: PMC2040167
NLM abbreviation: Mol Cell Neurosci
ISSN: 1044-7431
eISSN: 1095-9327
Grant note: DC02961 / NIDCD NIH HHS R01 DC002961-11A1 / NIDCD NIH HHS R01 DC002961 / NIDCD NIH HHS
Language: English
Date published: 09/2007
Academic Unit: Biology; Otolaryngology
Record Identifier: 9984217415602771

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