Related Experiment Video

Updated: Dec 28, 2025

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

12.2K

The Rab5 activator RME-6 is required for amyloid precursor protein endocytosis depending on the YTSI motif

Simone Eggert1, Tomas Gruebl1, Ritu Rajender1

  • 1Department of Human Biology and Human Genetics, Technical University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany.

Cellular and Molecular Life Sciences : CMLS
|February 18, 2020
PubMed

Insights

Alzheimer's disease research reveals a new pathway for amyloid precursor protein (APP) endocytosis. The study identifies Rab5 activator RME-6 and PAT1a protein as key regulators in APP internalization, impacting β-amyloid generation.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Endocytosis of amyloid precursor protein (APP) is crucial for β-amyloid production, a hallmark of Alzheimer's disease.
  • While the NPTY motif's role in APP endocytosis is known, the YTSI motif's function remains debated.

Purpose of the Study:

  • To investigate the role of the YTSI motif in APP endocytosis.
  • To identify novel proteins involved in APP internalization and their mechanisms.

Main Methods:

  • Utilized APP mutants lacking specific motifs (ΔYTSI, ΔNPTY).
  • Employed biochemical assays to demonstrate protein-protein interactions (PAT1a and RME-6).
  • Utilized knockdown and overexpression techniques to assess the functional impact of RME-6 and PAT1a on APP endocytosis.

Main Results:

  • APP lacking the YTSI motif showed reduced endocytosis, similar to the NPTY mutant.
  • The YTSI-binding protein PAT1a was found to interact with Rab5 activator RME-6.
  • RME-6 modulated APP endocytosis, with its knockdown decreasing and overexpression increasing internalization rates.
  • RME-6's effect on APP endocytosis was dependent on PAT1a.

Conclusions:

  • Identified RME-6 as a novel regulator of APP endocytosis.
  • Established a functional link between RME-6, PAT1a, and the YTSI motif in APP internalization.
  • Findings provide new insights into the molecular mechanisms governing APP processing and potential therapeutic targets for Alzheimer's disease.
Keywords:
Basolateral sorting signalClathrin-dependent endocytosisGDP–GTP exchange factorProtein interacting with APP tail 1SortingTrafficking

More Related Videos

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag08:55

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

15.9K
A Simple Fluorescence-based Reporter Assay to Identify Cellular Components Required for Ricin Toxin A Chain RTA Trafficking in Yeast09:03

A Simple Fluorescence-based Reporter Assay to Identify Cellular Components Required for Ricin Toxin A Chain RTA Trafficking in Yeast

Published on: December 15, 2017

8.4K

Related Concept Videos

Rab Cascades01:25

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
3.3K
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...
4.9K
Amyloid Fibrils03:03

Amyloid Fibrils

6.2K
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
11.5K
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...
4.9K
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
16.4K