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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 on the membrane, called clathrin pits, selectively recognize and bind the macromolecule to be internalized.

Adaptor proteins:

The clathrin vesicle coat comprises two distinct complexes, namely adaptor complex and cage complex. First, clathrin adaptor complexes such as AP1–5, AP180, and the Golgi-localized ARF-binding proteins are recruited to the clathrin pits. The adaptor proteins and other coat constituents serve in cargo selection, packaging, and vesicle formation. The adaptor proteins vary according to membrane type. The best-characterized adaptor proteins include AP1, which occurs in the trans-Golgi network and endosomal membrane, and AP2, which localizes in the plasma membrane. Thus, adaptor complexes link the membrane, membrane-embedded proteins, and cage proteins.

Cage complex:

The Clathrin proteins get recruited to the membrane after the adaptor protein. They form meshwork or lattices that make up the vesicle "cage." The main structural components of the cage complex are Clathrin heavy and light chains. The clathrin heavy chain consists of a long polypeptide comprising an N-terminal βpropeller domain and stretches of α helices. Together, they assemble into a long solenoid that bends into a rod-like structure. These bent rods trimerize to create a triskelion at the C terminus domain. The three arms of the triskelion extend up to 50 nm in length and are the ideal building material for a protein cage. An individual triskelion intertwines with the same number of other triskelions through its arms, ensuring that each triskelion represents a symmetrical vertex of the clathrin cage. The flexibility of the triskelion arms helps achieve the size variation required for different cargo.

Budding and uncoating:

Once the adaptor protein and the cage complex get recruited to the membrane, the adaptor protein is positioned between the clathrin cage and membrane. With the cargo loaded, coated pits invaginate into the cytoplasm and pinch off the plasma membrane. After a vesicle buds off, the clathrin coat is lost. The uncoated vesicle arrives at its destination organelle and fuses with its target membrane to deliver the cargo.

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