Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport

Manser, Catherine, Stevenson, Alison, Banner, Steven, Davies, Jennifer, Tudor, Elizabeth L, Ono, Yoshitaka, Leigh, P Nigel, McLoughlin, Declan M, Shaw, Christopher E and Miller, Christopher C J (2008) Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport. FEBS letters, 582 (15). pp. 2303-8. ISSN 0014-5793

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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

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User: Patricia Butler
Date Deposited: 14 Nov 2012 17:50
Last Modified: 14 Nov 2012 17:50
URI: http://sro.sussex.ac.uk/id/eprint/42520
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