biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...

, caveolae (

Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...

for "little caves"; singular, caveola), which are a special type of

lipid raft The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial ...

, are small (50–100 nanometer)

invagination Invagination is the process of a surface folding in on itself to form a cavity, pouch or tube. In developmental biology, invagination is a mechanism that takes place during gastrulation. This mechanism or cell movement happens mostly in the vegeta ...

s of the plasma membrane in the cells of many

vertebrates Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...

. They are the most abundant surface feature of many vertebrate cell types, especially

endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

cells, adipocytes and embryonic notochord cells. They were originally discovered by E. Yamada in 1955. These flask-shaped structures are rich in

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s as well as

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...

s such as

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

and

sphingolipid Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because o ...

s and have several functions in signal transduction. They are also believed to play a role in mechanoprotection,

mechanosensation Mechanosensation is the transduction of mechanical stimuli into neural signals. Mechanosensation provides the basis for the senses of light touch, hearing, proprioception, and pain. Mechanoreceptors found in the skin, called cutaneous mechanorecept ...

, endocytosis,

oncogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...

, and the uptake of

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...

and certain

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...

es.

Caveolins

Formation and maintenance of caveolae was initially thought to be primarily due to caveolin, a 21 kD protein. There are three homologous genes of caveolin expressed in mammalian cells: Cav1, Cav2 and Cav3. These proteins have a common topology: cytoplasmic N-terminus with scaffolding domain, long hairpin transmembrane domain and cytoplasmic C-terminus. Caveolins are synthesized as monomers and transported to the Golgi apparatus. During their subsequent transport through the secretory pathway, caveolins associate with lipid rafts and form oligomers (14-16 molecules). These oligomerized caveolins form the caveolae. The presence of caveolin leads to a local change in morphology of the membrane.

Cavins

Cavin proteins emerged in the late 2000s to be the main structural components controlling caveola formation. The cavin protein family consists of Cavin1 (also known as PTRF), Cavin2 (also known as SDPR), Cavin3 (also known as SRBC) and Cavin4 (also known as MURC). Cavin1 has been shown to be the main regulator of caveola formation in multiple tissues, with the sole expression of Cavin1 sufficient for morphological caveola formation in cells lacking caveolae but abundant in Cav1. Cavin4, analogous to Cav3, is muscle-specific.

Caveolar endocytosis

Caveolae are one source of

clathrin Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When ...

-independent raft-dependent endocytosis. The ability of caveolins to oligomerize due to their oligomerization domains is necessary for formation of caveolar endocytic vesicles. The oligomerization leads to formation of caveolin-rich microdomains in the plasma membrane. Increased levels of cholesterol and insertion of the scaffolding domains of caveolins into the plasma membrane leads to the expansion of the caveolar invagination and the formation of endocytic vesicles. Fission of the vesicle from the plasma membrane is then mediated by GTPase dynamin II, which is localized at the neck of the budding vesicle. The released caveolar vesicle can fuse with early endosome or caveosome. The caveosome is an endosomal compartment with neutral pH which does not have early endosomal markers. However, it contains molecules internalized by the caveolar endocytosis. This type of endocytosis is used, for example, for transcytosis of albumin in endothelial cells or for internalization of the insulin receptor in primary adipocytes.

Other roles of caveolae

*Caveolae have been shown to be required for the protection of cells from mechanical stress in multiple tissue types such as the skeletal muscles, endothelial cells and notochord cells. *Caveolae can be used for entry to the cell by some pathogens and so they avoid degradation in lysosomes. However, some bacteria do not use typical caveolae but only caveolin-rich areas of the plasma membrane. The pathogens exploiting this endocytic pathway include viruses such as SV40 and polyoma virus and bacteria such as some strains of ''Escherichia coli'', ''Pseudomonas aeruginosa'' and ''Porphyromonas gingivalis''. *Caveolae have a role in the cell signaling, too. Caveolins associate with some signaling molecules (e.g. eNOS) through their scaffolding domain and so they can regulate their signaling. Caveolae are also involved in regulation of channels and in calcium signaling. *Caveolae also participate in lipid regulation. High levels of caveolin Cav1 are expressed in adipocytes. Caveolin associates with cholesterol, fatty acids and lipid droplets and is involved in its regulation. *Caveolae can also serve as mechanosensors in various cell types. In endothelial cells, caveolae are involved in flow sensation. Chronic exposure to the flow stimulus leads to increased levels of caveolin Cav1 in plasma membrane, its phosphorylation, activation of eNOS signaling enzyme and to remodeling of blood vessels. In smooth-muscle cells, caveolin Cav1 has a role in stretch sensing which triggers cell-cycle progression.

Inhibitors

Some known inhibitors of the caveolae pathway are

Filipin Filipin is a mixture of chemical compounds first isolated by chemists at the Upjohn company in 1955 from the mycelium and culture filtrates of a previously unknown actinomycete, '' Streptomyces filipinensis''. It was discovered in a soil sample c ...

III,

Genistein Genistein (C15H10O5) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen. It was first isolated in 1899 from the dyer's bro ...

and

Nystatin Nystatin, sold under the brandname Mycostatin among others, is an antifungal medication. It is used to treat '' Candida'' infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be ...

References

External links

* {{Vesicular transport proteins Cell anatomy