Clathrin

Clathrin is a protein which plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975.^[1] It forms a triskelion shape which is composed of three clathrin heavy chains and three light chains. When the triskelion interact they form a polyhedral lattice which surrounds the vesicle.

Structure

Clathrin molecule in its triskelion form. N-terminal domain (blue) and proximal leg domain (red).   Clathrin coat structure

The clathrin triskelion is composed of three clathrin heavy chains and three light chains interacting at their C-termini. The three heavy chains provide the structural backbone of the clathrin lattice and the three light chains are thought to regulate the formation and disassembly of a clathrin lattice. Clathrin heavy chain is conceptually broken down into multiple subdomains, starting with the N-terminal domain, followed by the ankle, distal leg, knee, proximal leg, and trimerization domains. The N-terminal domain consists of a seven bladed β-propeller structure. The other domains form a super helix of short alpha helices. This was originally determined from the structure of the proximal leg domain which identified and is composed of a smaller structural module referred to as clathrin heavy chain repeat motifs. The light chains bind primarily to the proximal leg portion of the heavy chain with some interaction near the trimerization domain. When triskelia assemble together in solution, they can interact with enough flexibility to form 6-sided rings that yield a flatter lattice, or 5-sided rings which are necessary for curved lattice formation. When many triskelions connect they can form a basket-like structure.

Function

Clathrin facilitates the formation of small vesicles in the cytoplasm. Clathrin-coated vesicles selectively sort cargo at the cell membrane, trans-Golgi network and endosomal compartments for multiple membrane traffic pathways. After a vesicle buds into the cytoplasm the coat rapidly disassembles allowing the clathrin to recycle while the vesicle gets transported to a variety of locations. Adaptor molecules are responsible for self assembly and recruitment. Two examples of adaptor proteins are AP180^[2] and epsin.^[3][4][5] AP180 is used in synaptic vesicle formation. It recruits clathrin to membranes and also promotes its polymerization. Epsin also recruits clathrin to membranes and promotes its polymerization, and can help deform the membrane, and thus clathrin-coated vesicles can bud. In a cell, a triskelion floating in the cytoplasm binds to an adaptor protein, linking one of its feet to the membrane at a time. The skelion will bind to other ones attached to the membrane to form a polyhedral lattice, skelion which pulls the membrane into a bud. The skelion does not bind directly to the membrane, but binds to the adaptor proteins that recognize the molecules on the membrane surface.

Clathrin has another function aside from the coating of organelles. In non-dividing cells the formation of clathrin-coated vesicles occurs continuously. Formation of clathrin-coated vesicles is shut-down in cells undergoing mitosis. During mitosis, clathrin binds to the spindle apparatus. Clathrin aids in the congression of chromosomes by stabilizing fibres of the mitotic spindle. Clathrin is bound directly through the amino-terminal domain of the clathrin heavy chain. During mitosis the clathrin binds directly to the microtubules or microtubule-associated proteins. The stabilization of kinetochore fibres requires the trimetric structure of clathrin in order to strengthen the spindle fibres.^[6]

See also

• AP180
• Cap formation
• Cell migration
• Endocytic cycle
• Epsin
• Synaptic vesicle
• Adaptin

References

External links

• Clathrin structure
• Membrane Dynamics
• Clathrin-mediated endocytosis ASCB Image & Video Library

Further reading