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Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport
Author(s) -
Manser Catherine,
Stevenson Alison,
Banner Steven,
Davies Jennifer,
Tudor Elizabeth L.,
Ono Yoshitaka,
Nigel Leigh P.,
McLoughlin Declan M.,
Shaw Christopher E.,
Miller Christopher C.J.
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.05.034
Subject(s) - neurofilament , axoplasmic transport , neuroscience , amyotrophic lateral sclerosis , microbiology and biotechnology , cyclin dependent kinase 5 , chemistry , biology , kinase , medicine , protein kinase a , immunology , disease , mitogen activated protein kinase kinase , immunohistochemistry
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.