Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I

Gary A Wayman; Stefanie Kaech; Wilmon F Grant; Monika Davare; Soren Impey; Hiroshi Tokumitsu; Naohito Nozaki; Gary Banker; Thomas R Soderling

doi:10.1523/JNEUROSCI.3294-03.2004

Back

Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I

Journal article

Open access

Peer reviewed

Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I

Gary A Wayman, Stefanie Kaech, Wilmon F Grant, Monika Davare, Soren Impey, Hiroshi Tokumitsu, Naohito Nozaki, Gary Banker and Thomas R Soderling

The Journal of neuroscience, Vol.24(15), pp.3786-3794

04/14/2004

DOI: https://doi.org/10.1523/JNEUROSCI.3294-03.2004

Handle:

https://hdl.handle.net/2376/107233

PMCID: PMC6729350

PMID: 15084659

Files and links (1)

url

https://doi.org/10.1523/JNEUROSCI.3294-03.2004View

Published (Version of record) Open

Abstract

Protein Kinases - metabolism

Protein Kinases - genetics

Axons - enzymology

Calcium-Calmodulin-Dependent Protein Kinase Type 4

Axons - physiology

Pseudopodia - drug effects

Isoquinolines - pharmacology

Transfection

Genes, Dominant

Protein-Serine-Threonine Kinases - antagonists & inhibitors

Calcium-Calmodulin-Dependent Protein Kinase Type 1

Calcium-Calmodulin-Dependent Protein Kinase Type 2

Protein-Serine-Threonine Kinases - metabolism

Animals, Newborn

Growth Cones - physiology

Calcium-Calmodulin-Dependent Protein Kinases - genetics

Cells, Cultured

Enzyme Inhibitors - pharmacology

Protein-Serine-Threonine Kinases - genetics

Axons - drug effects

Naphthalimides

Rats

Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors

Rats, Sprague-Dawley

Growth Cones - enzymology

Calcium-Calmodulin-Dependent Protein Kinase Kinase

Protein Kinase Inhibitors

Animals

Benzimidazoles - pharmacology

Growth Cones - drug effects

Pseudopodia - physiology

Calcium-Calmodulin-Dependent Protein Kinases - metabolism

Calcium and calmodulin (CaM) are important signaling molecules that regulate axonal or dendritic extension and branching. The Ca2+-dependent stimulation of neurite elongation has generally been assumed to be mediated by CaM-kinase II (CaMKII), although other members of the CaMK family are highly expressed in developing neurons. We have examined this assumption using a combination of dominant-negative CaMKs (dnCaMKs) and other specific CaMK inhibitors. Here we report that inhibition of cytosolic CaMKI, but not CaMKII or nuclear CaMKIV, dramatically decreases axonal outgrowth and branching in cultured neonatal hippocampal and postnatal cerebellar granule neurons. CaMKI is found throughout the cell cytosol, including the growth cone. Growth cones of neurons expressing dnCaMI or dnCaMKK, the upstream activator of CaMKI, exhibit collapsed morphology with a prominent reduction in lamellipodia. Live-cell imaging confirms that these morphological changes are associated with a dramatic decrease in growth cone motility. Treatment of neurons with 1,8-naphthoylene benzimidazole-3-carboxylic acid (STO-609), an inhibitor of CaMKK, causes a similar change in morphology and reduction in growth cone motility, and this inhibition can be rescued by transfection with an STO-609-insensitive mutant of CaMKK or by transfection with constitutively active CaMKI. These results identify CaMKI as a positive transducer of growth cone motility and axon outgrowth and provide a new physiological role for the CaMKK-CaMKI pathway.

Metrics

10 Record Views

Details

Title: Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I
Creators: Gary A Wayman - Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239-3011, USA
Stefanie Kaech
Wilmon F Grant
Monika Davare
Soren Impey
Hiroshi Tokumitsu
Naohito Nozaki
Gary Banker
Thomas R Soderling
Publication Details: The Journal of neuroscience, Vol.24(15), pp.3786-3794
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: NS17112 / NINDS NIH HHS R01 NS027037 / NINDS NIH HHS DK44239 / NIDDK NIH HHS P01 DK044239 / NIDDK NIH HHS R01 NS017112 / NINDS NIH HHS NS27037 / NINDS NIH HHS
Identifiers: 99900547012401842
Language: English
Resource Type: Journal article