Related Experiment Video

Updated: Mar 22, 2026

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
11:05

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells

Published on: February 21, 2019

9.7K

The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb

Miao Sun1, Suwaiba Z Asghar1, Huaye Zhang1

  • 1Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States.

Neurobiology of Disease
|April 14, 2016
PubMed

Insights

Cell polarity protein Par3 regulates amyloid precursor protein (APP) processing and trafficking, crucial in Alzheimer's disease (AD) pathogenesis. Reduced Par3 in AD patients leads to increased Aβ accumulation, highlighting Par3 as a potential therapeutic target.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Alzheimer's disease (AD) pathogenesis involves amyloid precursor protein (APP) processing into β-amyloid peptide (Aβ).
  • Dysregulation in APP and secretase trafficking significantly alters APP processing in AD.
  • Cell polarity proteins are increasingly recognized for their roles in neurodegenerative diseases.

Purpose of the Study:

  • To investigate the role of the cell polarity protein Par3 in APP processing and trafficking.
  • To determine the impact of Par3 expression levels on Aβ production and APP localization.
  • To elucidate the molecular mechanisms by which Par3 influences APP metabolism.

Main Methods:

  • Analysis of Par3 expression in post-mortem brain tissue from AD patients.
  • Cellular models overexpressing or depleting Par3 to study APP processing.
  • Immunofluorescence and biochemical assays to track APP trafficking and Aβ levels.
  • Investigating the interaction between Par3, Numb, and APP using co-immunoprecipitation.

Main Results:

  • Full-length Par3 expression is significantly decreased in Alzheimer's disease patients.
  • Par3 overexpression enhances non-amyloidogenic APP processing, while Par3 depletion increases intracellular Aβ accumulation.
  • Loss of Par3 leads to decreased surface APP and promotes its targeting to the late endosome/lysosome pathway.
  • Par3's effects are mediated by its interference with the Numb-APP interaction.

Conclusions:

  • Par3 plays a critical role in regulating APP processing and trafficking.
  • Reduced Par3 expression is associated with pathological hallmarks of Alzheimer's disease.
  • Targeting Par3 or its downstream effectors represents a potential therapeutic strategy for AD.
Keywords:
Alzheimer diseaseAmyloid precursor protein (APP)Amyloid-β (Aβ)Cell polarityNumbPar3Trafficking

More Related Videos

Live-cell Imaging of Endocytic Transport using Functionalized Nanobodies in Cultured Cells08:02

Live-cell Imaging of Endocytic Transport using Functionalized Nanobodies in Cultured Cells

Published on: October 17, 2025

1.1K
The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking08:51

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking

Published on: February 12, 2022

4.0K

Related Concept Videos

Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
4.7K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
4.0K
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
6.6K
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
4.0K
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
5.4K