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From Proteopedia

Generalities

Clathrin is a 3 legged cytoplasmic protein with 3 and 3 . Its molecular weight is 273 985 Da.It has a triskelion shape (A tryskelion consists of three bent limbs radiating from a centre) and can self-assembled into a polyhedral structure arround [vesicles] of eukaryotic cells. Triskelia can polymerize into cages or even flat lattices, depending on the ratio hexagons/pentagons formed during the process.

Function

Communication between the different compartiments of eukaryotic cell and plasma membrane is allowed by vesicles, which convey molecules (called cargos) within the cytoplasm. Clathrin are involved in the formation of those vesicles in a process named clathrin-mediated endocytosis. However this process refers only to intake through vesicles from the plasma membrane.It has a large range of functions : regulating the surface expression of proteins, sampling the cell’s environment for growth and guidance cues, bringing nutrients into cells and controlling the activation of signalling pathways, retrieving proteins deposited after vesicle fusion and turning over membrane components by sending these components for degradation in lysosomes. Clathrins form a skeleton around the vesicle once several triskelia are assembled. The coated vesicle like so formed will then lose its round protein skeleton after its departure from the initial compartment because the clathrin cage is quickly dismantled. This phenomena proceeds through five stages: initiation, cargo selection, coat assembly, scission and uncoating. During the cargo selection and the initiation, clathrins polymerize into hexagons and pentagons. The ratio between these two shapes depends of the cells' curve.

Relevance

Endocytosis is essential to neurotransmission, as well to signal transduction and more generally to the regulation of many plasma membrane activities and is thus essential to eukaryotic life. Indeed, clathrins are shown as a active player in the recycling of synaptics vesicles, they are nessecary to the good functionement of synaptic transmission.

Structural highlights

To bind to the plasma membrane or to cargo receptors clathrin cage adopts a basket shape which is not spontaneous. This assembly requires adaptor proteins, complexes (such as AP2[[1]]) and accessory proteins (such as AP180 and epsin). All of them are recruited by the plasma membrane. AP2 proteins recruit directly from the cytsol clathrin triskelia which polymerize in hexagons and pentagons to form the clathrin coat around the nascent pit of shaped membrane. During the scission phase, GTPase dynamin[[2]] allows the scission at the neck of the nascent vesicle through the hydrolysis of its GTP. This zone where the membrane has been dissociated after the departure of the coated vesicle is left uncoated by clathrin. The defect in the clathrin cage thereby formed will ease the start of the uncoating process. Then, Cyclin G-associated kinase (GAK) recruit the ATPase heat shock cognate 70 (HSC70[[3]]) to disassemble the clathrin coat and leave the vesicle. The proteins that formed the previous apparatus are freed and recycle for the next endocytosis cycle.

References

1.Molecular mechanism and physiological functions of clathrin‑mediated endocytosisVOLUME 12 | AUGUST 2011 Harvey T. McMahon and Emmanuel Boucrot VOLUME 12 | AUGUST 2011