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Related Concept Videos

Phosphorylation01:02

Phosphorylation

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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...
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Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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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...
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Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
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Overview of Secretory Vesicles01:33

Overview of Secretory Vesicles

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Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
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Related Experiment Video

Updated: Jan 10, 2026

Modified Roller Tube Method for Precisely Localized and Repetitive Intermittent Imaging During Long-term Culture of Brain Slices in an Enclosed System
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Modified Roller Tube Method for Precisely Localized and Repetitive Intermittent Imaging During Long-term Culture of Brain Slices in an Enclosed System

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Aβ Modulates Extracellular Vesicles Proteomic Profile Impacting Phosphorylation Mediators.

Margarida Vaz1, Tânia Soares Martins1, Diogo Trigo1

  • 1Neuroscience and Signalling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal.

Molecular Neurobiology
|November 26, 2025
PubMed
Summary

Extracellular vesicles (EVs) in Alzheimer's disease (AD) models carry proteins involved in phosphorylation. Amyloid-beta (Aβ) treatment alters EV proteomes, highlighting GSK3β and phosphatases, suggesting EVs' role in AD progression.

Keywords:
Alzheimer’s diseaseAmyloid-βGSK3βMass spectrometryN2a cellsPhosphorylationProteome

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Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase

Published on: June 24, 2025

481

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is marked by amyloid-beta (Aβ) plaques and tau tangles.
  • Extracellular vesicles (EVs) are increasingly implicated in AD pathogenesis.
  • Understanding EV cargo in AD is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To investigate the proteomic changes in neuronal EVs under AD-mimicking conditions.
  • To identify key proteins and pathways affected by Aβ treatment within EVs.
  • To explore the role of EVs in the phosphorylation dynamics relevant to AD.

Main Methods:

  • Isolation of EVs from N2a cells treated with Aβ.
  • Mass spectrometry to analyze the EV proteome.
  • Bioinformatic and network analysis to identify protein interactions and pathways.
  • Assays to monitor GSK3β and protein phosphatase activity within EVs.

Main Results:

  • Aβ treatment altered the proteome of neuronal EVs, affecting proteins involved in signal transduction, protein modification, and cellular dynamics.
  • Enrichment or depletion of proteins related to cytoskeletal and mitochondrial function, calcium signaling, and Aβ metabolism was observed.
  • Glycogen synthase kinase 3β (GSK3β) emerged as a central node in the Aβ-affected EV proteome network.
  • EVs from Aβ-treated cells contained significantly different levels and activity of GSK3β and protein phosphatases compared to controls.

Conclusions:

  • Neuronal EVs carry proteins crucial for phosphorylation dynamics, including GSK3β and phosphatases.
  • Aβ treatment significantly modifies the proteomic cargo and activity of EVs, suggesting a role in AD progression.
  • Altered EV proteomes offer potential biomarkers and therapeutic targets for Alzheimer's disease.