clathrin-mediated endocytosis

Definition: Clathrin-mediated endocytosis is a vesicular transport event involved in the internalization and recycling of receptors participating in signal transduction events and nutrient import as well as in the reformation of synaptic vesicles.

Clathrin-mediated endocytosis is the specific uptake of large extracellular molecules such as proteins, membrane localized receptors and ion-channels. These receptors are associated with the cytosolic protein clathrin, which initiates the formation of a vesicle by forming a crystalline coat on the inner surface of the cell’s membrane.

The major route for endocytosis in most cells, and the best-understood, is that mediated by the molecule clathrin. This large protein assists in the formation of a coated pit on the inner surface of the plasma membrane of the cell. This pit then buds into the cell to form a coated vesicle in the cytoplasm of the cell. In so doing, it brings into the cell not only a small area of the surface of the cell but also a small volume of fluid from outside the cell.

Vesicles selectively concentrate and exclude certain proteins during formation and are not representative of the membrane as a whole. AP2 adaptors are multisubunit complexes that perform this function at the plasma membrane.

The best-understood receptors that are found concentrated in coated vesicles of mammalian cells are the LDL receptor (which removes LDL from the blood circulation), the transferrin receptor (which brings ferric ions bound by transferrin into the cell) and certain hormone receptors (such as that for EGF).

At any one moment, about 2% of the plasma membrane of a fibroblast is made up of coated pits. As a coated pit has a life of about a minute before it buds into the cell, a fibroblast takes up its surface by this route about once every 50 minutes.

Coated vesicles formed from the plasma membrane have a diameter of about 100nm and a lifetime measured in a few seconds. Once the coat has been shed, the remaining vesicle fuses with endosomes and proceeds down the endocytic pathway.

The actual budding-in process, whereby a pit is converted to a vesicle, is carried out by clathrin assisted by a set of cytoplasmic proteins, which includes dynamin and adaptors such as adaptin.

See also

 clathrin-coated vesicle formation
 interactions at the cytosol-membrane interface
 clathrin-coated vesicle assembly
 nucleation of clathrin-coated pits

References

 Roth MG. Clathrin-mediated endocytosis before fluorescent proteins. Nat Rev Mol Cell Biol. 2006 Jan;7(1):63-8. PMID: 16365635

 Kaksonen M, Toret CP, Drubin DG. Harnessing actin dynamics for clathrin-mediated endocytosis. Nat Rev Mol Cell Biol. 2006 Jun;7(6):404-14. PMID: 16723976

 Brooksbank C. Endocytosis. Tent pegs for clathrin. Nat Rev Mol Cell Biol. 2001 Mar ;2(3):166. PMID : 11265244

 McPherson PS. The endocytic machinery at an interface with the actin cytoskeleton : a dynamic, hip intersection. Trends Cell Biol. 2002 Jul ;12(7):312-5. PMID : 12185847

 Takei K, Haucke V. Clathrin-mediated endocytosis: membrane factors pull the trigger. Trends Cell Biol. 2001 Sep;11(9):385-91. PMID: 11514193