endocytosis

A cell engulfs a foreign substance through endocytosis, a form of active transport. During endocytosis, the cell membrane puckers up, forms a pouch around materials outside the cell, and pinches off to become a vesicle. If the contents need to be destroyed, lysosomes combine with the vesicle and release their enzymes.

Types

There are three types of endocytosis:

 clathrin-independent endocytosis (non-clathrin endocytic pathways)

• macropinocytosis
• caveolar endocytosis

 clathrin-mediated endocytosis

Clathrin-independent endocytosis (non-clathrin endocytic pathways)

 Macropinocytosis

Macropinocytosis is the invagination of the cell membrane to form a pocket, which then pinches off into the cell to form a vesicle filled with extracellular fluid (and molecules within it). The filling of the pocket occurs in a non-specific manner. The vesicle then travels into the cytosol and fuses with other vesicles such as endosomes and lysosomes.

 Caveolar endocytosis

Caveolae consist of the protein caveolin-1 with a bilayer enriched in cholesterol and glycolipids. Caveolae are flask-shape pits in the membrane that resemble the shape of a cave (hence the name caveolae). Uptake of extracellular molecules are also believed to be specifically mediated via receptors in caveolae.

Clathrin-mediated endocytosis

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

 endocytic pathway
 endosomes (endocytic vesicles)

• clathrin-dependent endocytosis
  • clathrin-containing endosomes

• clathrin-independent endocytosis
  • clathrin-independent endosomes
  • non-clathrin endocytic pathways
  • caveosomes (caveolin-1-containing endosomes)

 phagocytosis

References

 Soldati T, Schliwa M. Powering membrane traffic in endocytosis and recycling. Nat Rev Mol Cell Biol. 2006 Dec;7(12):897-908. PMID: 17139330

 Perret E, Lakkaraju A, Deborde S, Schreiner R, Rodriguez-Boulan E. Evolving endosomes: how many varieties and why?
Curr Opin Cell Biol. 2005 Aug;17(4):423-34. PMID: 15975780

 Nichols B. Caveosomes and endocytosis of lipid rafts.
J Cell Sci. 2003 Dec 1;116(Pt 23):4707-14. PMID: 14600257
References

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J Cell Sci. 2003 Dec 1;116(Pt 23):4707-14. PMID: 14600257

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 Nichols BJ, Lippincott-Schwartz J. Endocytosis without clathrin coats. Trends Cell Biol. 2001 Oct;11(10):406-12. PMID: 11567873

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

 Gruenberg J, Maxfield FR. Membrane transport in the endocytic pathway. Curr Opin Cell Biol 1995;7:552-563

 Mellman I. Endocytosis and molecular sorting. Annu Rev Cell Dev Biol 1996;12:575-625.

 Betz WJ, Mao F, Smith CB. Imaging exocytosis and endocytosis. Curr Opin Neurobiol. 1996 Jun;6(3):365-71. PMID: 8794083