Structural Proteins

Clathrin

Endocytosis plays a critical role in cellular functions ranging from nutrient acquisition to synaptic transmission. Receptor-mediated endocytosis allows the specific removal of cell surface receptors and their cargo from the plasma membrane and targets them to endosomes, where they are sorted for downregulation or recycling. It is widely assumed that coated vesicles mediate the selective transfer of molecules and membrane components between specific membranous organelles within cells. Clathrin is the main constituent of the polygonal network that forms the coat of coated vesicles and coated pits. In all cell types, clathrin-coated vesicles are responsible for receptor-mediated endocytosis at the plasma membrane and for the receptor-mediated sorting of lysosomal enzymes from trans-Golgi membranes to a pre-lysosomal compartment. In cells with a regulated secretory pathway, clathrin-coated membranes are involved in the formation of secretory granules and in the rapid uptake of plasma membrane following degranulation. A number of protein-protein and protein-lipid interactions underlie the assembly of the clathrin-based endocytic machine. In addition to clathrin, AP-2, and in neurons AP180, the proteins include dynamin and amphiphysin. Accessory cytosolic proteins include synaptojanin I, an inositol 5-phosphatase, and Eps15. Formation of clathrin-coated pits initiates the budding of clathrin-coated vesicles from membranes. These vesicles selectively remove receptors from a donor membrane and facilitate their transport to an intracellular target membrane with which the uncoated vesicle fuses. At each site, clathrin associates indirectly with the membrane by binding to an adaptor protein (AP) which interacts with the cytoplasmic domains of transmembrane receptors. Polymerization of clathrin then concentrates adaptors, associated receptors and their bound ligands into a coated vesicles.

Clathrin has a three-legged structure termed triskelion. The triskelion consists of three heavy chain polypeptides, each bound to a light chain (LC) of which there are two different types, LCa and LCb. The clathrin heavy chain is known to provide the backbone for the clathrin lattice. CHC is composed of a terminal globular domain, a distal segment and a proximal segment containing a LC binding site. Clathrin light chains contain regulatory domains that influence the recruitment, assembly, and disassembly of clathrin within the cell. 

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