Please use this identifier to cite or link to this item: https://doi.org/10.1091/mbc.E07-03-0237
Title: Inhibition of Pin1 reduces glutamate-induced perikaryal accumulation of phosphorylated neurofilament-H in neurons
Authors: Kesavapany, S. 
Patel, V.
Zheng, Y.-L.
Pareek, T.K.
Bjelogrlic, M.
Albers, W.
Amin, N.
Jaffe, H.
Gutkind, J.S.
Strong, M.J.
Grant, P.
Pant, H.C.
Issue Date: Sep-2007
Source: Kesavapany, S., Patel, V., Zheng, Y.-L., Pareek, T.K., Bjelogrlic, M., Albers, W., Amin, N., Jaffe, H., Gutkind, J.S., Strong, M.J., Grant, P., Pant, H.C. (2007-09). Inhibition of Pin1 reduces glutamate-induced perikaryal accumulation of phosphorylated neurofilament-H in neurons. Molecular Biology of the Cell 18 (9) : 3645-3655. ScholarBank@NUS Repository. https://doi.org/10.1091/mbc.E07-03-0237
Abstract: Under normal conditions, the proline-directed serine/threonine residues of neurofilament tail-domain repeats are exclusively phosphorylated in axons. In pathological conditions such as amyotrophic lateral sclerosis (ALS), motor neurons contain abnormal perikaryal accumulations of phosphorylated neurofilament proteins. The precise mechanisms for this compartment-specific phosphorylation of neurofilaments are not completely understood. Although localization of kinases and phosphatases is certainly implicated, another possibility involves Pin1 modulation of phosphorylation of the proline-directed serine/threonine residues. Pin1, a prolyl isomerase, selectively binds to phosphorylated proline-directed serine/threonine residues in target proteins and isomerizes cis isomers to more stable trans configurations. In this study we show that Pin1 associates with phosphorylated neurofilament-H (p-NF-H) in neurons and is colocalized in ALS-affected spinal cord neuronal inclusions. To mimic the pathology of neurodegeneration, we studied glutamate-stressed neurons that displayed increased p-NF-H in perikaryal accumulations that colocalized with Pin1 and led to cell death. Both effects were reduced upon inhibition of Pin1 activity by the use of an inhibitor juglone and down-regulating Pin1 levels through the use of Pin1 small interfering RNA. Thus, isomerization of lys-ser-pro repeat residues that are abundant in NF-H tail domains by Pin1 can regulate NF-H phosphorylation, which suggests that Pin1 inhibition may be an attractive therapeutic target to reduce pathological accumulations of p-NF-H. © 2007 by The American Society for Cell Biology.
Source Title: Molecular Biology of the Cell
URI: http://scholarbank.nus.edu.sg/handle/10635/120812
ISSN: 10591524
DOI: 10.1091/mbc.E07-03-0237
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

41
checked on Feb 21, 2018

WEB OF SCIENCETM
Citations

38
checked on Dec 13, 2017

Page view(s)

27
checked on Feb 24, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.