Caveolin

Last updated
Caveolin
Identifiers
SymbolCaveolin
Pfam PF01146
InterPro IPR001612
PROSITE PDOC00930
Caveolin 1, caveolae protein, 22kDa
Identifiers
Symbol CAV1
Alt. symbolsCAV
NCBI gene 857
HGNC 1527
OMIM 601047
RefSeq NM_001753
UniProt Q03135
Other data
Locus Chr. 7 q31
Caveolin 2
Identifiers
Symbol CAV2
NCBI gene 858
HGNC 1528
OMIM 601048
RefSeq NM_001233
UniProt P51636
Other data
Locus Chr. 7 q31
Caveolin 3
Identifiers
Symbol CAV3
NCBI gene 859
HGNC 1529
OMIM 601253
RefSeq NM_001234
UniProt P56539
Other data
Locus Chr. 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'.

Contents

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

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

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

Cancer

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

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

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

Related Research Articles

In biology, caveolae, which are a special type of lipid raft, are small invaginations of the plasma membrane, and the most abundant surface feature of, many vertebrate cell types in many vertebrate cell types, especially in endothelial cells, adipocytes and embryonic notochord cells. They were originally discovered by E. Yamada in 1955.

Dysferlin Protein encoded by the DYSF gene in humans

Dysferlin also known as dystrophy-associated fer-1-like protein is a protein that in humans is encoded by the DYSF gene.

Perlecan

Perlecan (PLC) also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the HSPG2 gene.

Caveolin 3

Caveolin-3 is a protein that in humans is encoded by the CAV3 gene. Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites.

Dystroglycan

Dystroglycan is a protein that in humans is encoded by the DAG1 gene.

Utrophin

Utrophin is a protein that in humans is encoded by the UTRN gene.

Low-density lipoprotein receptor-related protein 8 Cell surface receptor, part of the low-density lipoprotein receptor family

Low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), is a protein that in humans is encoded by the LRP8 gene. ApoER2 is a cell surface receptor that is part of the low-density lipoprotein receptor family. These receptors function in signal transduction and endocytosis of specific ligands. Through interactions with one of its ligands, reelin, ApoER2 plays an important role in embryonic neuronal migration and postnatal long-term potentiation. Another LDL family receptor, VLDLR, also interacts with reelin, and together these two receptors influence brain development and function. Decreased expression of ApoER2 is associated with certain neurological diseases.

Originally identified as Kirsten ras associated gene (krag), Sarcospan (SSPN) is a 25-kDa transmembrane protein located in the dystrophin-associated protein complex of skeletal muscle cells, where it is most abundant. It contains four transmembrane spanning helices with both N- and C-terminal domains located intracellularly. Loss of SSPN expression occurs in patients with Duchenne muscular dystrophy. Dystrophin is required for proper localization of SSPN. SSPN is also an essential regulator of Akt signaling pathways. Without SSPN, Akt signaling pathways will be hindered and muscle regeneration will not occur.

Dystrobrevin is a protein that binds to dystrophin in the costamere of skeletal muscle cells. In humans, there are at least two isoforms of dystrobrevin, dystrobrevin alpha and dystrobrevin beta.

Caveolin 1 Protein-coding gene in the species Homo sapiens

Caveolin-1 is a protein that in humans is encoded by the CAV1 gene.

RAS p21 protein activator 1

RAS p21 protein activator 1 or RasGAP, also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:

KHDRBS1

KH domain-containing, RNA-binding, signal transduction-associated protein 1 is a protein that in humans is encoded by the KHDRBS1 gene.

Laminin, alpha 2

Laminin subunit alpha-2 is a protein that in humans is encoded by the LAMA2 gene.

Integrin alpha 7

Alpha-7 integrin is a protein that in humans is encoded by the ITGA7 gene. Alpha-7 integrin is critical for modulating cell-matrix interactions. Alpha-7 integrin is highly expressed in cardiac muscle, skeletal muscle and smooth muscle cells, and localizes to Z-disc and costamere structures. Mutations in ITGA7 have been associated with congenital myopathies and noncompaction cardiomyopathy, and altered expression levels of alpha-7 integrin have been identified in various forms of muscular dystrophy.

FLOT1

Flotillin-1 is a protein that in humans is encoded by the FLOT1 gene.

FLOT2

Flotillin-2 is a protein that in humans is encoded by the FLOT2 gene. Flotillin 2 (flot-2) is a highly conserved protein isolated from caveolae/lipid raft domains that tether growth factor receptors linked to signal transduction pathways. Flot-2 binds to PAR-1, a known upstream mediator of major signal transduction pathways implicated in cell growth and metastasis, and may influence tumour progression.

Caveolin 2

Caveolin-2 is a protein that in humans is encoded by the CAV2 gene.

GNA11

Guanine nucleotide-binding protein subunit alpha-11 is a protein that in humans is encoded by the GNA11 gene. Together with GNAQ, it functions as a Gq alpha subunit.

Inner nuclear membrane protein

Inner nuclear membrane proteins are membrane proteins that are embedded in or associated with the inner membrane of the nuclear envelope. There are about 60 INM proteins, most of which are poorly characterized with respect to structure and function. Among the few well-characterized INM proteins are lamin B receptor (LBR), lamina-associated polypeptide 1 (LAP1), lamina-associated polypeptide-2 (LAP2), emerin and MAN1.

Patched (Ptc) is a conserved 12-pass transmembrane protein receptor that plays an obligate negative regulatory role in the Hedgehog signaling pathway in insects and vertebrates. Patched is an essential gene in embryogenesis for proper segmentation in the fly embryo, mutations in which may be embryonic lethal. Patched functions as the receptor for the Hedgehog protein and controls its spatial distribution, in part via endocytosis of bound Hedgehog protein, which is then targeted for lysosomal degradation.

References

  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. S2CID   23034625.
  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. S2CID   35611697.
  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.
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