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Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport
journal contribution
posted on 2023-06-08, 13:41 authored by Catherine Manser, Alison Stevenson, Steven Banner, Jennifer Davies, Elizabeth L Tudor, Yoshitaka Ono, Nigel LeighNigel Leigh, Declan M McLoughlin, Christopher E Shaw, Christopher C J MillerNeurofilaments 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
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Publication status
- Published
Journal
FEBS lettersISSN
0014-5793Publisher
ElsevierExternal DOI
Issue
15Volume
582Page range
2303-8Department affiliated with
- Clinical and Experimental Medicine Publications
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- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-11-14Usage metrics
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