Journal article
Transient Receptor Potential Canonical 5 Channels Activate Ca2+/Calmodulin Kinase Iγ to Promote Axon Formation in Hippocampal Neurons
The Journal of neuroscience, Vol.29(31), pp.9794-9808
08/05/2009
Handle:
https://hdl.handle.net/2376/104615
PMID: 19657032
Abstract
Functionality of neurons is dependent on their compartmentalized polarization of dendrites and an axon. The rapid and selective outgrowth of one neurite, relative to the others, to form the axon is critical in initiating neuronal polarity. Axonogenesis is regulated in part by an optimal intracellular calcium concentration. Our investigation of Ca
2+
-signaling pathways involved in axon formation using cultured hippocampal neurons demonstrates a role for Ca
2+
/calmodulin kinase kinase (CaMKK) and its downstream target Ca
2+
/calmodulin kinase I (CaMKI). Expression of constitutively active CaMKI induced formation of multiple axons, whereas blocking CaMKK or CaMKI activity with pharmacological, dominant-negative, or short hairpin RNA (shRNA) methods significantly inhibited axon formation. CaMKK signals via the γ-isoform of CaMKI as shRNA to CaMKIγ, but not the other CaMKI isoforms, inhibited axon formation. Furthermore, overexpression of wild-type CaMKIγ, but not a mutant incapable of membrane association, accelerated the rate of axon formation. Pharmacological or small interfering RNA inhibition of transient receptor potential canonical 5 (TRPC5) channels, which are present in developing axonal growth cones, suppressed CaMKK-mediated activation of CaMKIγ as well as axon formation. We demonstrate using biochemical fractionation and immunocytochemistry that CaMKIγ and TRPC5 colocalize to lipid rafts. These results are consistent with a model in which highly localized calcium influx through the TRPC5 channels activates CaMKK and CaMKIγ, which subsequently promote axon formation.
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Details
- Title
- Transient Receptor Potential Canonical 5 Channels Activate Ca2+/Calmodulin Kinase Iγ to Promote Axon Formation in Hippocampal Neurons
- Creators
- Monika A Davare - Vollum Institute andDale A Fortin - Vollum Institute andTakeo Saneyoshi - National Institute of Advanced Industrial Science and Technology, Biological Information Research Center, Aomi, Tokyo 135-0064, Japan, andSean Nygaard - Vollum Institute andStefanie Kaech - Jungers Center, Oregon Health & Science University, Portland, Oregon 97223Gary Banker - Jungers Center, Oregon Health & Science University, Portland, Oregon 97223Thomas R Soderling - Vollum Institute andGary A Wayman - Department of Veterinary Comparative Anatomy, Physiology and Pharmacology, Washington State University, Pullman, Washington 99163
- Publication Details
- The Journal of neuroscience, Vol.29(31), pp.9794-9808
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Society for Neuroscience
- Identifiers
- 99900546637301842
- Language
- English
- Resource Type
- Journal article