Related Experiment Video

Updated: Mar 9, 2026

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
07:55

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP

Published on: October 17, 2015

12.4K

Amyloid precursor protein traffics from the Golgi directly to early endosomes in an Arl5b- and AP4-dependent pathway

Wei Hong Toh1, Jing Zhi A Tan1, Khalisah L Zulkefli1

  • 1Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia.

Traffic (Copenhagen, Denmark)
|December 22, 2016
PubMed

Insights

Newly synthesized amyloid precursor protein (APP) is directly transported from the Golgi to early endosomes, bypassing cell surface transport. This pathway regulates APP processing and amyloid-beta (Aβ) peptide generation.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Molecular Biology

Background:

  • Amyloid precursor protein (APP) processing generates amyloid-beta (Aβ) peptides, implicated in neurodegenerative diseases.
  • The intracellular transport of APP from the Golgi to the endolysosomal system is crucial for its processing by secretases (BACE1 and γ-secretase).

Purpose of the Study:

  • To elucidate the post-Golgi transport pathway of newly synthesized APP.
  • To identify key molecular players regulating APP trafficking and its impact on Aβ generation.

Main Methods:

  • Immunofluorescence microscopy to track APP localization.
  • Depletion studies using siRNA to assess the roles of Arl5b and AP4.
  • Biochemical assays to measure APP processing and Aβ secretion.

Main Results:

  • Newly synthesized APP is primarily transported from the trans-Golgi network (TGN) directly to early endosomes, with minimal cell surface presence.
  • Arl5b, a TGN-localized small G protein, and AP4 are essential for this direct APP transport to early endosomes.
  • Depletion of Arl5b or AP4 leads to Golgi accumulation of APP, increased APP processing, and elevated Aβ secretion.

Conclusions:

  • The TGN serves as a critical sorting station for APP, directing it towards early endosomes for processing.
  • Arl5b and AP4 mediate a direct TGN-to-early endosome pathway for APP, influencing Aβ production.
  • This trafficking route represents a key regulatory point for APP processing and Aβ generation.
Keywords:
AP4Arl5bamyloid precursor proteinamyloid-β peptideanterograde transportearly endosomestrans-Golgi network

More Related Videos

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells11:05

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
Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain10:08

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

Published on: August 28, 2012

12.3K

Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.4K
Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
8.0K
The Early Endosome: Endocytosis of Transferrin01:28

The Early Endosome: Endocytosis of Transferrin

Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
5.0K
Clathrin Coated Vesicles01:12

Clathrin Coated Vesicles

Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
9.8K
Overview of Protein Sorting and Transport01:45

Overview of Protein Sorting and Transport

Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation.  In gated transport, folded...
23.3K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.6K