Caveolin

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Caveolin
Identifiers
SymbolCaveolin
PfamPF01146
InterProIPR001612
PROSITEPDOC00930
Caveolin 1, caveolae protein, 22kDa
Identifiers
SymbolCAV1
Alt. symbolsCAV
NCBI gene857
HGNC1527
OMIM601047
RefSeqNM_001753
UniProtQ03135
Other data
LocusChr. 7 q31
Caveolin 2
Identifiers
SymbolCAV2
NCBI gene858
HGNC1528
OMIM601048
RefSeqNM_001233
UniProtP51636
Other data
LocusChr. 7 q31
Caveolin 3
Identifiers
SymbolCAV3
NCBI gene859
HGNC1529
OMIM601253
RefSeqNM_001234
UniProtP56539
Other data
LocusChr. 3 p25

In molecular biology caveolins are a family of integral membrane proteins that are the principal components of caveolae membranes and involved in receptor-independent endocytosis.[1][2][3] Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signaling molecules. They also induce positive (inward) membrane curvature by way of oligomerization, and hairpin insertion. Various classes of signaling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain'.

The caveolin gene family has three members in vertebrates: CAV1, CAV2, and CAV3, coding for the proteins caveolin-1, caveolin-2, and caveolin-3, respectively. All three members are membrane proteins with similar structure. Caveolin forms oligomers and associates with cholesterol and sphingolipids in certain areas of the cell membrane, leading to the formation of caveolae.

Structure and expression[edit]

The caveolins are similar in structure. They all form hairpin loops that are inserted into the cell membrane. Both the C-terminus and the N-terminus face the cytoplasmic side of the membrane. There are two isoforms of caveolin-1: caveolin-1α and caveolin-1β, the latter lacking a part of the N-terminus.

Caveolins are found in the majority of adherent, mammalian cells.

Function[edit]

The functions of caveolins are still under intensive investigation. They are best known for their role in the formation of 50-nanometer-size invaginations of the plasma membrane, called caveolae. Oligomers of caveolin form the coat of these domains. Cells that lack caveolins also lack caveolae. Many functions are ascribed to these domains, ranging from endocytosis and transcytosis to signal transduction.

Caveolin-1 has also been shown to play a role in the integrin signaling. The tyrosine phosphorylated form of caveolin-1 colocalizes with focal adhesions, suggesting a role for caveolin-1 in migration. Indeed, downregulation of caveolin-1 leads to less efficient migration in vitro.

Genetically engineered mice that lack caveolin-1 and caveolin-2 are viable and fertile, showing that neither the caveolins nor the caveolae are essential in embryonic development or reproduction of these animals. However, knock-out animals do develop abnormal, hypertrophic lungs, and cardiac myopathy, leading to a reduction in lifespan. Mice lacking caveolins also suffer from impaired angiogenic responses as well as abnormal responses to vasoconstrictive stimuli. In zebrafish, lack of caveolins leads to embryonic lethality, suggesting that higher vertebrates (as exemplified by mice) have developed compensation or redundancy for the functions of caveolins.

Role in disease[edit]

Cancer[edit]

Caveolins have a paradoxical role in the development of this disease. They have been implicated in both tumor suppression and oncogenesis.[4] High expression of caveolins leads to inhibition of cancer-related pathways, such as growth factor signaling pathways. However, certain cancer cells that express caveolins have been shown to be more aggressive and metastatic, because of a potential for anchorage-independent growth.

Cardiovascular diseases[edit]

Caveolins are thought to play an important role during the development of atherosclerosis.[5] Furthermore, caveolin-3 has been associated with long QT syndrome.[6]

Muscular dystrophy[edit]

Caveolin-3 has been implicated in the development of certain types of muscular dystrophy (limb-girdle muscular dystrophy).[7]

References[edit]

  1. ^ Tang Z, Scherer PE, Okamoto T, Song K, Chu C, Kohtz DS, Nishimoto I, Lodish HF, Lisanti MP (January 1996). "Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle". J. Biol. Chem. 271 (4): 2255–61. doi:10.1074/jbc.271.4.2255. PMID 8567687.
  2. ^ Scherer PE, Okamoto T, Chun M, Nishimoto I, Lodish HF, Lisanti MP (January 1996). "Identification, sequence, and expression of caveolin-2 defines a caveolin gene family". Proc. Natl. Acad. Sci. U.S.A. 93 (1): 131–5. doi:10.1073/pnas.93.1.131. PMC 40192. PMID 8552590.
  3. ^ Williams TM, Lisanti MP (2004). "The caveolin proteins". Genome Biol. 5 (3): 214. doi:10.1186/gb-2004-5-3-214. PMC 395759. PMID 15003112.
  4. ^ Shatz M, Liscovitch M (March 2008). "Caveolin-1: a tumor-promoting role in human cancer". Int. J. Radiat. Biol. 84 (3): 177–89. doi:10.1080/09553000701745293. PMID 18300018.
  5. ^ Williams TM, Lisanti MP (2004). "The Caveolin genes: from cell biology to medicine". Ann. Med. 36 (8): 584–95. doi:10.1080/07853890410018899. PMID 15768830.
  6. ^ Vatta M, Ackerman MJ, Ye B, Makielski JC, Ughanze EE, Taylor EW, Tester DJ, Balijepalli RC, Foell JD, Li Z, Kamp TJ, Towbin JA (November 2006). "Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome". Circulation. 114 (20): 2104–12. doi:10.1161/CIRCULATIONAHA.106.635268. PMID 17060380.
  7. ^ Galbiati F, Razani B, Lisanti MP (October 2001). "Caveolae and caveolin-3 in muscular dystrophy". Trends Mol Med. 7 (10): 435–41. doi:10.1016/S1471-4914(01)02105-0. PMID 11597517.

External links[edit]