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Related Concept Videos

Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
Receptor-Mediated Endocytosis01:20

Receptor-Mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
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...
ER Retrieval Pathway01:45

ER Retrieval Pathway

In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...

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Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis
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Intracellular receptor/ligand sorting based on endosomal retention components.

A R French1, D A Lauffenburger

  • 1Department of Chemical Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.

Biotechnology and Bioengineering
|August 5, 1996
PubMed
Summary

A mathematical model explains how cells sort endocytosed molecules. It shows that selective receptor retention within endosomes, modulated by receptor occupancy, governs sorting outcomes for epidermal growth factor (EGF) and its receptor.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Mathematical Modeling

Background:

  • Endocytosed molecules are sorted to various cellular destinations from endosomes.
  • General principles of endosomal sorting remain poorly understood.
  • Previous studies show diverse sorting outcomes for different ligands and receptors.

Purpose of the Study:

  • To develop a mechanistic mathematical model for endosomal sorting.
  • To test the hypothesis that selective receptor retention and occupancy modulate sorting.
  • To explain varied sorting outcomes observed with the epidermal growth factor (EGF)/receptor system.

Main Methods:

  • Developed a mechanistic mathematical model of endosomal sorting.
  • Incorporated selective receptor retention and receptor occupancy as key mechanisms.
  • Applied the model to the epidermal growth factor (EGF)/receptor system in fibroblasts.

Main Results:

  • A single mechanism of selective retention can account for diverse sorting outcomes.
  • The model predicts deviations from fluid-phase sorting due to selective retention.
  • Three distinct sorting regimes emerge based on ligand concentration and retention.

Conclusions:

  • Selective endosomal retention of receptor/ligand complexes is a key sorting principle.
  • Receptor occupancy modulates the influence of selective retention.
  • The model provides a framework for understanding endosomal sorting and predicts distinct sorting regimes.