Caveolae

In biology, caveolae (Latin for "little caves"; singular, caveola), which are a special type of lipid raft, are small (50–100 nanometer) invaginations of the plasma membrane in many vertebrate cell types, especially in endothelial cells, adipocytes and embryonic notochord cells.[1] They were originally discovered by E. Yamada in 1955.[2]

These flask-shaped structures are rich in proteins as well as lipids such as cholesterol and sphingolipids and have several functions in signal transduction.[3] They are also believed to play a role in mechanoprotection, mechanosensation, endocytosis, oncogenesis, and the uptake of pathogenic bacteria and certain viruses.[4][5][6][7]

Caveolins
Main article: caveolin

Formation and maintenance of caveolae was initially thought to be primarily due to caveolin,[8] 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.[9]

Cavins

Cavin proteins emerged in the late 2000s to be the main structural components controlling caveola formation.[10][11][12][13] 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.[14][10] Cavin4, analogous to Cav3, is muscle-specific.[11]

Caveolar endocytosis

Caveolae are one source of clathrin-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.[9][15]

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.[9]

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 [16][17][18].
  • 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.[15]
  • 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.[15]
  • 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.[15]
  • 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.[15]

Inhibitors

Some known inhibitors of the caveolae pathway are Filipin III, Genistein and Nystatin.[9]

gollark: There is, in fact, no escape.
gollark: --tel hangup
gollark: Æ emergency mitigation time.
gollark: OH NO
gollark: Heavserver has *excellent* bots.

See also

References
  1. Nixon, Susan J.; Carter, Adrian; Wegner, Jeremy; Ferguson, Charles; Floetenmeyer, Matthias; Riches, Jamie; Key, Brian; Westerfield, Monte; Parton, Robert G. (2007-07-01). "Caveolin-1 is required for lateral line neuromast and notochord development" (PDF). Journal of Cell Science. 120 (13): 2151–2161. doi:10.1242/jcs.003830. ISSN 0021-9533. PMID 17550965.
  2. Li, Xiang-An; Everson, William V.; Smart, Eric J. (2005). "Caveolae, Lipid Rafts, and Vascular Disease". Trends in Cardiovascular Medicine. 15 (3): 92–6. doi:10.1016/j.tcm.2005.04.001. PMID 16039968.
  3. Anderson RG (1998). "The caveolae membrane system". Annu. Rev. Biochem. 67: 199–225. doi:10.1146/annurev.biochem.67.1.199. PMID 9759488.
  4. Parton, Robert G.; del Pozo, Miguel A. (2013-02-01). "Caveolae as plasma membrane sensors, protectors and organizers". Nature Reviews Molecular Cell Biology. 14 (2): 98–112. doi:10.1038/nrm3512. ISSN 1471-0072. PMID 23340574.
  5. Frank P, Lisanti M (2004). "Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia". Current Opinion in Lipidology. 15 (5): 523–9. doi:10.1097/00041433-200410000-00005. PMID 15361787.
  6. Li X, Everson W, Smart E (2005). "Caveolae, lipid rafts, and vascular disease". Trends Cardiovasc Med. 15 (3): 92–6. doi:10.1016/j.tcm.2005.04.001. PMID 16039968.
  7. Pelkmans L (2005). "Secrets of caveolae- and lipid raft-mediated endocytosis revealed by mammalian viruses". Biochim Biophys Acta. 1746 (3): 295–304. doi:10.1016/j.bbamcr.2005.06.009. PMID 16126288.
  8. Caveolae at the US National Library of Medicine Medical Subject Headings (MeSH)
  9. Lajoie, P. and I.R. Nabi, Lipid rafts, caveolae, and their endocytosis. Int Rev Cell Mol Biol, 2010. 282: p. 135-63.
  10. Hill, Michelle M.; Bastiani, Michele; Luetterforst, Robert; Kirkham, Matthew; Kirkham, Annika; Nixon, Susan J.; Walser, Piers; Abankwa, Daniel; Oorschot, Viola M. J. (2008-01-11). "PTRF-cavin, a conserved cytoplasmic protein required for caveola formation and function". Cell. 132 (1): 113–124. doi:10.1016/j.cell.2007.11.042. ISSN 0092-8674. PMC 2265257. PMID 18191225.
  11. Bastiani, Michele; Liu, Libin; Hill, Michelle M.; Jedrychowski, Mark P.; Nixon, Susan J.; Lo, Harriet P.; Abankwa, Daniel; Luetterforst, Robert; Fernandez-Rojo, Manuel (2009-06-29). "MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes" (PDF). The Journal of Cell Biology. 185 (7): 1259–1273. doi:10.1083/jcb.200903053. ISSN 0021-9525. PMC 2712963. PMID 19546242.
  12. Kovtun, Oleksiy; Tillu, Vikas A.; Ariotti, Nicholas; Parton, Robert G.; Collins, Brett M. (2015-04-01). "Cavin family proteins and the assembly of caveolae". Journal of Cell Science. 128 (7): 1269–1278. doi:10.1242/jcs.167866. ISSN 0021-9533. PMC 4379724. PMID 25829513.
  13. Parton, Robert G.; Collins, Brett M. (2016-12-13). "Unraveling the architecture of caveolae". Proceedings of the National Academy of Sciences. 113 (50): 14170–14172. doi:10.1073/pnas.1617954113. ISSN 0027-8424. PMC 5167180. PMID 27911845.
  14. Liu, Libin; Brown, Dennis; McKee, Mary; LeBrasseur, Nathan K.; Yang, Dan; Albrecht, Kenneth H.; Ravid, Katya; Pilch, Paul F. (2017-05-29). "Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia and glucose intolerance". Cell Metabolism. 8 (4): 310–317. doi:10.1016/j.cmet.2008.07.008. ISSN 1550-4131. PMC 2581738. PMID 18840361.
  15. Parton, R.G. and K. Simons, The multiple faces of caveolae. Nature Reviews Molecular Cell Biology, 2007. 8(3): p. 185-94.
  16. Lo, Harriet P; Hall, Thomas E; Parton, Robert G (2016-01-13). "Mechanoprotection by skeletal muscle caveolae". Bioarchitecture. 6 (1): 22–27. doi:10.1080/19490992.2015.1131891. ISSN 1949-0992. PMC 4914031. PMID 26760312.
  17. Cheng, Jade P.X.; Mendoza-Topaz, Carolina; Howard, Gillian; Chadwick, Jessica; Shvets, Elena; Cowburn, Andrew S.; Dunmore, Benjamin J.; Crosby, Alexi; Morrell, Nicholas W. (2015-10-12). "Caveolae protect endothelial cells from membrane rupture during increased cardiac output". The Journal of Cell Biology. 211 (1): 53–61. doi:10.1083/jcb.201504042. ISSN 0021-9525. PMC 4602045. PMID 26459598.
  18. Lim, Ye-Wheen; Lo, Harriet P.; Ferguson, Charles; Martel, Nick; Giacomotto, Jean; Gomez, Guillermo A.; Yap, Alpha S.; Hall, Thomas E.; Parton, Robert G. (2017-07-10). "Caveolae Protect Notochord Cells against Catastrophic Mechanical Failure during Development". Current Biology. 27 (13): 1968–1981.e7. doi:10.1016/j.cub.2017.05.067. ISSN 0960-9822. PMID 28648821.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.