Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport.
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Authors
Manser, Catherine
Stevenson, Alison
Banner, Steven
Davies, Jennifer
Tudor, Elizabeth L
Ono, Yoshitaka
Leigh, P Nigel
McLoughlin, Declan M
Shaw, Christopher E
Miller, Christopher C J
Issue Date
2008-06-02
Type
Journal Article
Research Support, Non-U.S. Gov't
Research Support, Non-U.S. Gov't
Language
en
Keywords
Alternative Title
Abstract
Neurofilaments are synthesised in neuronal cell bodies and then transported through axons. Damage to neurofilament transport is seen in amyotrophic lateral sclerosis (ALS). Here, we show that PKN1, a neurofilament head-rod domain kinase is cleaved and activated in SOD1G93A transgenic mice that are a model of ALS. Moreover, we demonstrate that glutamate, a proposed toxic mechanism in ALS leads to caspase cleavage and disruption of PKN1 in neurons. Finally, we demonstrate that a cleaved form of PKN1 but not wild-type PKN1 disrupts neurofilament organisation and axonal transport. Thus, deregulation of PKN1 may contribute to the pathogenic process in ALS.
Description
Citation
Manser, C., Stevenson, A., Banner, S., Davies, J., Tudor, E. L., Ono, Y., Leigh, P. N., McLoughlin, D. M., Shaw, C. E., & Miller, C. C. J. (2008). Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport. FEBS letters, 582(15), 2303–2308. https://doi.org/10.1016/j.febslet.2008.05.034
Publisher
License
Journal
FEBS letters
Volume
582
Issue
15
PubMed ID
ISSN
0014-5793