PINCH in the Cellular Stress Response to Tau-Hyperphosphorylation

Autor: William Yen, Jane Kovalevich, Dianne Langford, Rajnish S. Dave, Inna Rom, Radhika Adiga, Ahmet Y. Ozdemir
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
lcsh:Medicine
Gene Expression
Bioinformatics
Mice
0302 clinical medicine
Cellular stress response
Molecular Cell Biology
Phosphorylation
lcsh:Science
Cellular Stress Responses
Neurons
0303 health sciences
Multidisciplinary
biology
Signal transducing adaptor protein
Neurodegenerative Diseases
LIM Domain Proteins
Signaling Cascades
3. Good health
Ubiquitin ligase
Cell biology
Infectious Diseases
Mental Health
Neurology
Medicine
Female
Cellular Types
Microtubule-Associated Proteins
Research Article
Signal Transduction
Immunoprecipitation
Microtubule-associated protein
Ubiquitin-Protein Ligases
Mice
Transgenic
tau Proteins
Stress Signaling Cascade
03 medical and health sciences
Stress
Physiological
mental disorders
Gene silencing
Animals
Humans
Heat shock
Biology
030304 developmental biology
Adaptor Proteins
Signal Transducing
lcsh:R
Membrane Proteins
body regions
biology.protein
Synaptophysin
lcsh:Q
030217 neurology & neurosurgery
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 3, p e58232 (2013)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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