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Related Concept Videos

Clathrin Coated Vesicles01:12

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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...
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After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
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Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of...
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Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
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Updated: Jun 15, 2025

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Vesiculation pathways in clathrin-mediated endocytosis.

Xinran Wang1,2, Julien Berro3,4,5, Rui Ma1,2

  • 1Department of Physics, Xiamen University, Xiamen 361005, China.

Biorxiv : the Preprint Server for Biology
|August 26, 2024
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Summary

Clathrin-mediated endocytosis involves membrane deformation. This study reveals vesiculation pathways are a continuum, with a constant-area-like model best fitting experimental data for clathrin coat formation.

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Area of Science:

  • Cell biology
  • Biophysics

Background:

  • Clathrin-mediated endocytosis internalizes plasma membrane patches to form vesicles.
  • Two hypotheses, constant area and constant curvature, explain clathrin coat membrane deformation.
  • Previous experimental data could not distinguish between these hypotheses.

Purpose of the Study:

  • To investigate the continuum of clathrin coat vesiculation pathways.
  • To determine the most accurate model for membrane deformation during endocytosis.
  • To identify key experimental measurements for distinguishing between models.

Main Methods:

  • Developed a theoretical framework considering free energies of clathrin assembly and curvature generation.
  • Defined vesiculation pathways in the phase space of coating area and intrinsic curvature.
  • Compared model predictions with experimental data.

Main Results:

  • Clathrin-mediated endocytosis pathways form a continuum, not limited to constant area or constant curvature extremes.
  • The best fit to experimental data suggests an initial expansion of coating area followed by increased intrinsic curvature.
  • Differences in membrane morphology are most pronounced in the early stages of endocytosis.

Conclusions:

  • The constant curvature model is incompatible with experimental observations.
  • A constant-area-like pathway, with initial area expansion and later curvature increase, best describes clathrin-mediated endocytosis.
  • Measuring clathrin coat tip radius and projected area is crucial for model validation.