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Amyloid-beta-dependent phosphorylation of collapsin response mediator protein-2 dissociates kinesin in Alzheimer's disease Mokhtar, S, Kim, M, Magee, K, Mun Aui, P, Thomas, S, Bakhuraysah, M, Alrehaili, A, Young Lee, J, Steer, D, Kenny, R, McLean, C, Azari, M, Birpanagos, A, Lipiec, E, Heraud, P, Wood, B and Petratos, S 2018, 'Amyloid-beta-dependent phosphorylation of collapsin response mediator protein-2 dissociates kinesin in Alzheimer's disease', Neural Regeneration Research, vol. 13, no. 6, pp. 1066-1080. Document type: Journal Article Collection: Journal Articles Title Amyloid-beta-dependent phosphorylation of collapsin response mediator protein-2 dissociates kinesin in Alzheimer's disease Author(s) Mokhtar, S Kim, M Magee, K Mun Aui, P Thomas, S Bakhuraysah, M Alrehaili, A Young Lee, J Steer, D Kenny, R McLean, C Azari, M Birpanagos, A Lipiec, E Heraud, P Wood, B Petratos, S Year 2018 Journal name Neural Regeneration Research Volume number 13 Issue number 6 Start page 1066 End page 1080 Total pages 15 Publisher Medknow Publications and Media Pvt. Ltd. Abstract Alzheimers disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles. Prior to the development of these characteristic pathological hallmarks of AD, anterograde axonal transport is impaired. However, the key proteins that initiate these intracellular impairments remain elusive. The collapsin response mediator protein-2 (CRMP-2) plays an integral role in kinesin-1-dependent axonal transport and there is evidence that phosphorylation of CRMP-2 releases kinesin-1. Here, we tested the hypothesis that amyloid-beta (Aβ)-dependent phosphorylation of CRMP-2 disrupts its association with the kinesin-1 (an anterograde axonal motor transport protein) in AD. We found that brain sections and lysates from AD patients demonstrated elevated phosphorylation of CRMP-2 at the T555 site. Additionally, in the transgenic Tg2576 mouse model of familial AD (FAD) that exhibits Aβ accumulation in the brain with age, we found substantial co-localization of pT555CRMP-2 and dystrophic neurites. In SH-SY5Y differentiated neuronal cultures, Aβ-dependent phosphorylation of CRMP-2 at the T555 site was also elevated and this reduced the CRMP-2 association with kinesin-1. The overexpression of an unphosphorylatable form of CRMP-2 in neurons promoted the re-establishment of CRMP-2-kinesin association and axon elongation. These data suggest that Aβ-dependent phosphorylation of CRMP-2 at the T555 site may directly impair anterograde axonal transport protein function, leading to neuronal defects. Subject Central Nervous System Keyword(s) amyloid-beta protein collapsin response mediator protein kinases kinesin microtubules tubulin DOI - identifier 10.4103/1673-5374.233451 Copyright notice © 2018 Medknow Publications. All rights reserved. ISSN 1673-5374 Related Links Link Description https://dx.doi.org/10.4103/1673-5374.233451 Link to Published Version   Versions Version Filter Type Mon, 10 Dec 2018, 13:22:02 EST Filtered Full Citation counts:   Cited 7 times in Thomson Reuters Web of Science Article | Citations Cited 0 times in Scopus Article Altmetric details: Access Statistics: 33 Abstract Views  -  Detailed Statistics Created: Thu, 06 Dec 2018, 10:39:00 EST by Catalyst Administrator