Protein of the Month |
April 2007
MORE ON THIS MONTH’S PROTEIN
|
|
OTHER PROTEINS OF INTEREST |
|
Molecule of the Month: Clathrin |
|
|
Clathrin
By Jennifer McDowall
Once a protein is synthesised by ribosomes, and processed by the endoplasmic reticulum and Golgi apparatus, it then needs to be transported to the correct location within or outside the cell. Several proteins are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination. These include membrane proteins that cannot simply diffuse through the cytosol due to their hydrophobic nature, proteins destined for export out of the cell (such as neurotransmitters), and soluble vacuolar or lysosomal proteins, some of which are degradative enzymes that can be potentially harmful to the cell. All these proteins carry signal sequences that target them for transport along the secretory pathway. This traffic can be bidirectional, to ensure that proteins required to form the vesicles are recycled. In addition, proteins can be imported into a cell via the budding of a vesicle off the plasma membrane (endocytosis), which is the major route for extracellular hormone and signalling factor uptake, as well as for the internalisation of receptors and the recycling of pre- and post-synaptic membrane proteins. These various protein transport vesicles have specialised coat proteins, such as clathrin, which are important for cargo selection and for specifying the final destination. The formation of a clathrin coat is fundamental to the mechanism of vesicle budding as well as receptor sorting.
Clathrin,
moving proteins and lipids about
Clathrin-coated vesicles are found in all eukaryotic cells, but they are particularly enriched in the brain, where they play a major role in the formation of neurotransmitter-containing pre-synaptic vesicles required for synaptic nerve transmission. Clathrin-mediated endocytosis also regulates the number of receptors on a cell.
Pathogenic viruses and bacteria can gain entry into their target cell by making use of the host’s clathrin-dependent endocytic machinery, producing molecules on their surface that mimic endogenous ligands to the host’s cell receptors, thereby inducing the host’s intracellular signalling cascades.
Clathrin self-polymerises into a curved lattice around a vesicle as it buds from the TGN, plasma membrane or endosomes, this lattice acting to stabilise the vesicle and facilitate budding. Clathrin is a trimer composed of three heavy chains and three light chains, each monomer projecting outwards like a leg; this three-legged structure is known as a triskelion. Clathrin triskelia polymerise to form a cage-like lattice by twisting individual legs together. Each leg ends in an N-terminal beta-propeller structure (heavy chain) that can bind peptide motifs between its blades, while the C-terminal (heavy chain) forms the central hub of the triskelion. The multiple blades created when the triskelia polymerise are involved in multiple protein interactions, enabling the recruitment of different cargo adaptors and membrane attachment proteins. By concentrating different cargo adaptors on the clathrin lattice, a diverse array of protein and lipid cargo can be transported.