Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport |
| |
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 |
| |
Institution: | MRC Centre for Neurodegeneration Research, Department of Neuroscience P037, Institute of Psychiatry, King's College, De Crespigny Park, Denmark Hill, London, United Kingdom. |
| |
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. |
| |
Keywords: | PKN protein kinase N NFL NFM and NFH neurofilament light middle and heavy chains ALS amyotrophic lateral sclerosis |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|