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Related Concept Videos

Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...

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Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells
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Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells

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Phosphorylation differentiates tau-dependent neuronal toxicity and dysfunction.

Katerina Papanikolopoulou1, Stylianos Kosmidis, Sofia Grammenoudi

  • 1Institute of Cellular and Developmental Biology Biomedical Sciences Research Centre Alexander Fleming, Vari 16672, Greece.

Biochemical Society Transactions
|July 28, 2010
PubMed
Summary
This summary is machine-generated.

Specific tau phosphorylation sites, not overall hyperphosphorylation, drive tauopathy in a cell-type-specific manner. Blocking novel phosphorylation sites Ser(238) and Thr(245) caused profound mushroom body neuron dysfunction and impaired learning.

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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
09:22

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

Area of Science:

  • Neuroscience
  • Cell Biology
  • Genetics

Background:

  • Tauopathies exhibit heterogeneous pathology, with varying neuronal susceptibility.
  • Phosphorylation at specific sites, rather than general hyperphosphorylation, is implicated in tau toxicity.
  • Cell-type-specific effects of tau suggest distinct mechanisms of neuronal dysfunction.

Purpose of the Study:

  • To investigate the role of specific tau phosphorylation sites in neuronal dysfunction and degeneration.
  • To determine if novel phosphorylation sites mediate cell-type-specific tau toxicity in the central nervous system (CNS).
  • To differentiate the mechanisms underlying tau-dependent neuronal degeneration versus dysfunction.

Main Methods:

  • Utilized Drosophila melanogaster as a model organism to study tau accumulation in the CNS.
  • Investigated the impact of pan-neuronal tau expression on mushroom body (MB) neurons.
  • Analyzed the effects of specific phosphorylation site occupation (Ser(238) and Thr(245)) on MB structure and function.
  • Assessed associative learning defects in flies with altered tau phosphorylation patterns.

Main Results:

  • Pan-neuronal tau accumulation in Drosophila CNS selectively affected MB neurons, confirming cell-type specificity.
  • MB aberrations and impaired associative learning were linked to phosphorylation at Ser(238) and Thr(245).
  • Blocking these specific phosphorylation sites resulted in structurally normal but dysfunctional MBs and learning deficits.
  • Temporal restriction of tau accumulation altered phosphorylation patterns and led to similarly dysfunctional MBs.

Conclusions:

  • Tau toxicity and dysfunction are mediated by phosphorylation at specific sites in a cell-type-specific manner.
  • Novel phosphorylation sites Ser(238) and Thr(245) are critical for tau-induced MB dysfunction and learning impairment.
  • Distinct temporal dynamics of phosphorylation at these sites may underlie differential effects of tau on neuronal degeneration and dysfunction.