clathrin

Clathrin is a cytosolic protein essential for the formation of clathrin-coated vesicles, which mediate cargo sorting and membrane trafficking in eukaryotic cells. It plays a central role in clathrin-mediated endocytosis at the plasma membrane and in vesicular trafficking between the trans-Golgi network and endosomes.

Clathrin coats are built from triskelions, assemblies composed of three clathrin heavy chains and three clathrin light chains. The heavy chains form the curved lattice that shapes vesicles, while the light chains regulate assembly dynamics and stability. The clathrin lattice arranges into polyhedral geometries that enclose a vesicle.

Vesicle formation is initiated by adaptor protein complexes, most notably AP-2 at the plasma membrane and AP-1 at theGolgi. These adaptors link cargo receptors to the clathrin lattice, selecting specific cargo such as receptors and transporters. As assembly proceeds, the membrane curves and buds inward to form a vesicle. Dynamin, a GTPase, mediates scission to release the vesicle from the donor membrane. After separation, uncoating factors such as HSC70 and auxilin remove the clathrin coat to permit the vesicle to fuse with its target compartment.

Cargoes commonly transported by clathrin-coated vesicles include the transferrin receptor, LDL receptor, and various nutrient transporters. Beyond endocytosis, clathrin also facilitates trafficking from the Golgi to endosomes and from the Golgi to lysosomes, contributing to sorting of lysosomal enzymes and receptor recycling.

Clathrin is highly conserved across eukaryotes. Disruptions in clathrin-mediated pathways can impact receptor recycling, neurotransmitter release, and pathogen entry, as several viruses exploit clathrin-mediated endocytosis for cell entry.