PINCH in the cellular stress response to tau-hyperphosphorylation.
Particularly interesting new cysteine- histidine- rich protein (PINCH) is an adaptor protein that our data have shown is required for neurite extension under stressful conditions. Our previous studies also report that PINCH is recalled by neurons showing decreased levels of synaptodendritic signalin...
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doaj-79c8987f1f5f4059b402bea2ce2918af2020-11-25T02:25:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5823210.1371/journal.pone.0058232PINCH in the cellular stress response to tau-hyperphosphorylation.Ahmet Yunus OzdemirInna RomJane KovalevichWilliam YenRadhika AdigaRajnish S DaveDianne LangfordParticularly interesting new cysteine- histidine- rich protein (PINCH) is an adaptor protein that our data have shown is required for neurite extension under stressful conditions. Our previous studies also report that PINCH is recalled by neurons showing decreased levels of synaptodendritic signaling proteins such as MAP2 or synaptophysin in the brains of human immunodeficiency virus (HIV) patients. The current study addressed potential role(s) for PINCH in neurodegenerative diseases. Mass spectrometry predicted the interaction of PINCH with Tau and with members of the heat shock response. Our in vitro data confirmed that PINCH binds to hyperphosphorylated (hp) Tau and to E3 ubiquitin ligase, carboxy-terminus of heat shock-70 interacting protein. Silencing PINCH prior to induction of hp-Tau resulted in more efficient clearance of accumulating hp-Tau, suggesting that PINCH may play a role in stabilizing hp-Tau. Accumulation of hp-Tau is implicated in more than 20 neuropathological diseases including Alzheimer's disease (AD), frontotemporal dementia (FTD), and human immunodeficiency virus encephalitis (HIVE). Analyses of brain tissues from HIVE, AD and FTD patients showed that PINCH is increased and binds to hp-Tau. These studies address a new mechanism by which AD and HIV may intersect and identify PINCH as a contributing factor to the accumulation of hyperphosphorylated Tau.http://europepmc.org/articles/PMC3595241?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ahmet Yunus Ozdemir Inna Rom Jane Kovalevich William Yen Radhika Adiga Rajnish S Dave Dianne Langford |
spellingShingle |
Ahmet Yunus Ozdemir Inna Rom Jane Kovalevich William Yen Radhika Adiga Rajnish S Dave Dianne Langford PINCH in the cellular stress response to tau-hyperphosphorylation. PLoS ONE |
author_facet |
Ahmet Yunus Ozdemir Inna Rom Jane Kovalevich William Yen Radhika Adiga Rajnish S Dave Dianne Langford |
author_sort |
Ahmet Yunus Ozdemir |
title |
PINCH in the cellular stress response to tau-hyperphosphorylation. |
title_short |
PINCH in the cellular stress response to tau-hyperphosphorylation. |
title_full |
PINCH in the cellular stress response to tau-hyperphosphorylation. |
title_fullStr |
PINCH in the cellular stress response to tau-hyperphosphorylation. |
title_full_unstemmed |
PINCH in the cellular stress response to tau-hyperphosphorylation. |
title_sort |
pinch in the cellular stress response to tau-hyperphosphorylation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Particularly interesting new cysteine- histidine- rich protein (PINCH) is an adaptor protein that our data have shown is required for neurite extension under stressful conditions. Our previous studies also report that PINCH is recalled by neurons showing decreased levels of synaptodendritic signaling proteins such as MAP2 or synaptophysin in the brains of human immunodeficiency virus (HIV) patients. The current study addressed potential role(s) for PINCH in neurodegenerative diseases. Mass spectrometry predicted the interaction of PINCH with Tau and with members of the heat shock response. Our in vitro data confirmed that PINCH binds to hyperphosphorylated (hp) Tau and to E3 ubiquitin ligase, carboxy-terminus of heat shock-70 interacting protein. Silencing PINCH prior to induction of hp-Tau resulted in more efficient clearance of accumulating hp-Tau, suggesting that PINCH may play a role in stabilizing hp-Tau. Accumulation of hp-Tau is implicated in more than 20 neuropathological diseases including Alzheimer's disease (AD), frontotemporal dementia (FTD), and human immunodeficiency virus encephalitis (HIVE). Analyses of brain tissues from HIVE, AD and FTD patients showed that PINCH is increased and binds to hp-Tau. These studies address a new mechanism by which AD and HIV may intersect and identify PINCH as a contributing factor to the accumulation of hyperphosphorylated Tau. |
url |
http://europepmc.org/articles/PMC3595241?pdf=render |
work_keys_str_mv |
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