Editing Caveolae

{{short description|Type of lipid raft in endocytosis}}
In [[biology]], '''caveolae''' ([[Latin]] for "little caves"; singular, '''caveola'''), which are a special type of [[lipid raft]], are small (50–100 [[nanometer]]) [[invagination]]s of the [[plasma membrane]] in the [[Cell (biology)|cells]] of many [[vertebrate]]s. They are the most abundant surface feature of many vertebrate cell types, especially [[endothelium|endothelial]] cells, [[adipocyte]]s and [[Notochord|embryonic notochord cells]].<ref>{{cite journal |last1=Nixon |first1=Susan J. |last2=Carter |first2=Adrian |last3=Wegner |first3=Jeremy |last4=Ferguson |first4=Charles |last5=Floetenmeyer |first5=Matthias |last6=Riches |first6=Jamie |last7=Key |first7=Brian |last8=Westerfield |first8=Monte |last9=Parton |first9=Robert G. |title=Caveolin-1 is required for lateral line neuromast and notochord development |journal=Journal of Cell Science |date=1 July 2007 |volume=120 |issue=13 |pages=2151–2161 |doi=10.1242/jcs.003830 |pmid=17550965 |doi-access=free }}</ref><ref>{{cite journal |last1=Lo |first1=Harriet P |last2=Hall |first2=Thomas E |last3=Parton |first3=Robert G |title=Mechanoprotection by skeletal muscle caveolae |journal=BioArchitecture |date=13 January 2016 |volume=6 |issue=1 |pages=22–27 |doi=10.1080/19490992.2015.1131891 |pmid=26760312 |pmc=4914031 }}</ref> They were originally discovered by E. Yamada in 1955.<ref name="Li Everson Smart 2005">{{cite journal |last1=Li |first1=Xiang-An |last2=Everson |first2=William V. |last3=Smart |first3=Eric J. |title=Caveolae, Lipid Rafts, and Vascular Disease |journal=Trends in Cardiovascular Medicine |date=April 2005 |volume=15 |issue=3 |pages=92–96 |doi=10.1016/j.tcm.2005.04.001 |pmid=16039968 }}</ref>

These flask-shaped structures are rich in [[protein]]s as well as [[lipid]]s such as [[cholesterol]] and [[sphingolipid]]s and have several functions in [[signal transduction]].<ref>{{cite journal |last1=Anderson |first1=Richard G. W. |title=The caveolae membrane system |journal=Annual Review of Biochemistry |date=June 1998 |volume=67 |issue=1 |pages=199–225 |doi=10.1146/annurev.biochem.67.1.199 |pmid=9759488 |doi-access=free }}</ref> They are also believed to play a role in [[wikt:mechanoprotection|mechanoprotection]], [[mechanosensation]], [[endocytosis]], [[oncogenesis]], and the uptake of [[pathogen]]ic [[bacteria]] and certain [[virus]]es.<ref>{{cite journal |last1=Parton |first1=Robert G. |last2=del Pozo |first2=Miguel A. |title=Caveolae as plasma membrane sensors, protectors and organizers |journal=Nature Reviews Molecular Cell Biology |date=February 2013 |volume=14 |issue=2 |pages=98–112 |doi=10.1038/nrm3512 |pmid=23340574 |s2cid=21940682 }}</ref><ref>{{cite journal |last1=Frank |first1=Philippe G |last2=Lisanti |first2=Michael P |title=Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia |journal=Current Opinion in Lipidology |date=October 2004 |volume=15 |issue=5 |pages=523–529 |doi=10.1097/00041433-200410000-00005 |pmid=15361787 |s2cid=20778606 }}</ref><ref name="Li Everson Smart 2005"/><ref>{{cite journal |last1=Pelkmans |first1=Lucas |title=Secrets of caveolae- and lipid raft-mediated endocytosis revealed by mammalian viruses |journal=Biochimica et Biophysica Acta (BBA) - Molecular Cell Research |date=December 2005 |volume=1746 |issue=3 |pages=295–304 |doi=10.1016/j.bbamcr.2005.06.009 |pmid=16126288 |doi-access=free }}</ref>

==Caveolins==
{{main|Caveolin}}
Formation and maintenance of caveolae was initially thought to be primarily due to [[caveolin]],<ref>{{MeshName|Caveolae}}</ref> 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.<ref name="Lajoie & Nabi 2010">{{cite book |doi=10.1016/S1937-6448(10)82003-9 |title=Lipid Rafts, Caveolae, and Their Endocytosis |series=International Review of Cell and Molecular Biology |year=2010 |last1=Lajoie |first1=Patrick |last2=Nabi |first2=Ivan R. |volume=282 |pages=135–163 |pmid=20630468 |isbn=978-0-12-381256-8 }}</ref>

== Cavins ==
Cavin proteins emerged in the late 2000s to be the main structural components controlling caveola formation.<ref name="Hill Bastiani Luetterforst et al 2008">{{cite journal |last1=Hill |first1=Michelle M. |last2=Bastiani |first2=Michele |last3=Luetterforst |first3=Robert |last4=Kirkham |first4=Matthew |last5=Kirkham |first5=Annika |last6=Nixon |first6=Susan J. |last7=Walser |first7=Piers |last8=Abankwa |first8=Daniel |last9=Oorschot |first9=Viola M.J. |last10=Martin |first10=Sally |last11=Hancock |first11=John F. |last12=Parton |first12=Robert G. |title=PTRF-Cavin, a Conserved Cytoplasmic Protein Required for Caveola Formation and Function |journal=Cell |date=January 2008 |volume=132 |issue=1 |pages=113–124 |doi=10.1016/j.cell.2007.11.042 |pmid=18191225 |pmc=2265257 }}</ref><ref name="Bastiani Liu Hill et al 2009">{{cite journal |last1=Bastiani |first1=Michele |last2=Liu |first2=Libin |last3=Hill |first3=Michelle M. |last4=Jedrychowski |first4=Mark P. |last5=Nixon |first5=Susan J. |last6=Lo |first6=Harriet P. |last7=Abankwa |first7=Daniel |last8=Luetterforst |first8=Robert |last9=Fernandez-Rojo |first9=Manuel |last10=Breen |first10=Michael R. |last11=Gygi |first11=Steven P. |last12=Vinten |first12=Jorgen |last13=Walser |first13=Piers J. |last14=North |first14=Kathryn N. |last15=Hancock |first15=John F. |last16=Pilch |first16=Paul F. |last17=Parton |first17=Robert G. |title=MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes |journal=Journal of Cell Biology |date=29 June 2009 |volume=185 |issue=7 |pages=1259–1273 |doi=10.1083/jcb.200903053 |pmid=19546242 |pmc=2712963 |hdl=2144/3220 |hdl-access=free }}</ref><ref>{{cite journal |last1=Kovtun |first1=Oleksiy |last2=Tillu |first2=Vikas A. |last3=Ariotti |first3=Nicholas |last4=Parton |first4=Robert G. |last5=Collins |first5=Brett M. |title=Cavin family proteins and the assembly of caveolae |journal=Journal of Cell Science |date=1 April 2015 |volume=128 |issue=7 |pages=1269–1278 |doi=10.1242/jcs.167866 |pmid=25829513 |pmc=4379724 }}</ref><ref>{{cite journal |last1=Parton |first1=Robert G. |last2=Collins |first2=Brett M. |title=Unraveling the architecture of caveolae |journal=Proceedings of the National Academy of Sciences |date=13 December 2016 |volume=113 |issue=50 |pages=14170–14172 |doi=10.1073/pnas.1617954113 |pmid=27911845 |pmc=5167180 |bibcode=2016PNAS..11314170P |doi-access=free }}</ref> The cavin protein family consists of [[PTRF|Cavin1]] (also known as PTRF), [[SDPR|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.<ref>{{cite journal |last1=Liu |first1=Libin |last2=Brown |first2=Dennis |last3=McKee |first3=Mary |last4=LeBrasseur |first4=Nathan K. |last5=Yang |first5=Dan |last6=Albrecht |first6=Kenneth H. |last7=Ravid |first7=Katya |author-link7=Katya Ravid |last8=Pilch |first8=Paul F. |date=October 2008 |title=Deletion of Cavin/PTRF Causes Global Loss of Caveolae, Dyslipidemia, and Glucose Intolerance |journal=Cell Metabolism |volume=8 |issue=4 |pages=310–317 |doi=10.1016/j.cmet.2008.07.008 |pmc=2581738 |pmid=18840361}}</ref><ref name="Hill Bastiani Luetterforst et al 2008"/> Cavin4, analogous to Cav3, is muscle-specific.<ref name="Bastiani Liu Hill et al 2009"/>

==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.<ref name="Lajoie & Nabi 2010"/><ref name="Parton & Simons 2007"/>

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.<ref name="Lajoie & Nabi 2010"/>

==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.<ref>{{cite journal |last1=Lo |first1=Harriet P |last2=Hall |first2=Thomas E |last3=Parton |first3=Robert G |title=Mechanoprotection by skeletal muscle caveolae |journal=BioArchitecture |date=2 January 2016 |volume=6 |issue=1 |pages=22–27 |doi=10.1080/19490992.2015.1131891 |pmid=26760312 |pmc=4914031 }}</ref><ref>{{cite journal |last1=Cheng |first1=Jade P.X. |last2=Mendoza-Topaz |first2=Carolina |last3=Howard |first3=Gillian |last4=Chadwick |first4=Jessica |last5=Shvets |first5=Elena |last6=Cowburn |first6=Andrew S. |last7=Dunmore |first7=Benjamin J. |last8=Crosby |first8=Alexi |last9=Morrell |first9=Nicholas W. |last10=Nichols |first10=Benjamin J. |title=Caveolae protect endothelial cells from membrane rupture during increased cardiac output |journal=Journal of Cell Biology |date=12 October 2015 |volume=211 |issue=1 |pages=53–61 |doi=10.1083/jcb.201504042 |pmid=26459598 |pmc=4602045 }}</ref><ref>{{cite journal |last1=Lim |first1=Ye-Wheen |last2=Lo |first2=Harriet P. |last3=Ferguson |first3=Charles |last4=Martel |first4=Nick |last5=Giacomotto |first5=Jean |last6=Gomez |first6=Guillermo A. |last7=Yap |first7=Alpha S. |last8=Hall |first8=Thomas E. |last9=Parton |first9=Robert G. |title=Caveolae Protect Notochord Cells against Catastrophic Mechanical Failure during Development |journal=Current Biology |date=July 2017 |volume=27 |issue=13 |pages=1968–1981.e7 |doi=10.1016/j.cub.2017.05.067 |pmid=28648821 |doi-access=free |bibcode=2017CBio...27E1968L }}</ref>
* 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''.<ref name="Parton & Simons 2007">{{cite journal |last1=Parton |first1=Robert G. |last2=Simons |first2=Kai |title=The multiple faces of caveolae |journal=Nature Reviews Molecular Cell Biology |date=March 2007 |volume=8 |issue=3 |pages=185–194 |doi=10.1038/nrm2122 |pmid=17318224 |s2cid=10830810 }}</ref>
* Caveolae have a role in 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.<ref name="Parton & Simons 2007"/>
* 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 their regulation.<ref name="Parton & Simons 2007"/>
* 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.<ref name="Parton & Simons 2007"/>

==Inhibitors==
Some known inhibitors of the caveolae pathway are [[filipin]] III, [[genistein]] and [[nystatin]].<ref name="Lajoie & Nabi 2010"/>

==See also==
* [[Pinocytosis]]

==References==
{{reflist}}

==External links==
* {{BUHistology|21402loa}}

{{Structures of the cell membrane}}
{{Vesicular transport proteins}}

[[Category:Cell anatomy]]
[[Category:Eukaryotic cell anatomy]]