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{{short description|Polymer of tubulin that forms part of the cytoskeleton}}
[[File:Tubulin Infographic.jpg|alt=Tubulin and Microtubule Metrics Infographic|thumb|440x440px|Microtubule and tubulin metrics<ref>{{Cite web|url=https://puresoluble.com/digital-downloads/|title=Digital Downloads|website=PurSolutions|language=en-US|access-date=2020-02-20|archive-date=2022-09-29|archive-url=https://web.archive.org/web/20220929022306/https://puresoluble.com/digital-downloads/|url-status=live}}</ref>]]
'''Microtubules''' are [[polymer]]s of [[tubulin]] that form part of the [[cytoskeleton]] and provide structure and shape to [[eukaryotic]] cells. Microtubules can be as long as 50 [[micrometre]]s, as wide as 23 to 27 [[nanometer|nm]]<ref>{{cite journal | vauthors = Ledbetter MC, Porter KR | title = A "microtubule" in plant cell fine structure | journal = Journal of Cell Biology | volume = 19 | issue = 1 | pages = 239–50 | date = 1963 | pmid = 19866635 | pmc = 2106853 | doi = 10.1083/jcb.19.1.239 }}</ref> and have an inner diameter between 11 and 15 nm.<ref>{{cite journal | vauthors = Chalfie M, Thomson JN | title = Organization of neuronal microtubules in the nematode Caenorhabditis elegans. | journal = Journal of Cell Biology | volume = 82 | issue = 1 | pages = 278–89 | date = 1979 | pmid = 479300 | pmc = 2110421 | doi = 10.1083/jcb.82.1.278 }}</ref> They are formed by the polymerization of a [[Protein dimer|dimer]] of two [[globular protein]]s, [[Tubulin#Eukaryotic|alpha and beta tubulin]] into [[#Structure|protofilaments]] that can then associate laterally to form a hollow tube, the microtubule.<ref>{{cite web |url=https://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/microtub.htm | vauthors = Diwan JJ | date = 2006 |title= Microtubules | work = Rensselaer Polytechnic Institute |access-date=2014-02-24 |archive-url=https://web.archive.org/web/20140206072438/http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/microtub.htm |archive-date=2014-02-06 }}</ref> The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.[[File:Microtubules in the leading edge of a cell.tif|thumb|right|Microtubules are one of the cytoskeletal filament systems in eukaryotic cells. The microtubule cytoskeleton is involved in the transport of material within cells, carried out by motor proteins that move on the surface of the microtubule.]]
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== History ==
Tubulin and microtubule-mediated processes, like cell locomotion, were seen by early microscopists, like [[Leeuwenhoek]] (1677). However, the fibrous nature of flagella and other structures were discovered two centuries later, with improved [[light microscope]]s, and confirmed in the 20th century with the [[electron microscope]] and biochemical studies.<ref>Wayne, R. 2009. ''[https://books.google.com/books?id=t_biw80LgjwC Plant Cell Biology: From Astronomy to Zoology] {{Webarchive|url=https://web.archive.org/web/20240221025111/https://books.google.com/books?id=t_biw80LgjwC |date=2024-02-21 }}''. Amsterdam: Elsevier/Academic Press, p. 165.</ref>
''[[In vitro]]'' assays for microtubule [[motor protein]]s such as [[dynein]] and [[kinesin]] are researched by fluorescently tagging a microtubule and fixing either the microtubule or motor proteins to a microscope slide, then visualizing the slide with video-enhanced microscopy to record the travel of the motor proteins. This allows the movement of the motor proteins along the microtubule or the microtubule moving across the motor proteins.<ref>{{cite journal
== Structure ==
[[File:Tubulin dimer 1JFF.png|thumb|Cartoon representation of the structure of α(yellow)/β(red)-tubulin heterodimer, GTP and GDP.<ref>{{cite journal | vauthors = Löwe J, Li H, Downing KH, Nogales E | title = Refined structure of alpha beta-tubulin at 3.5 A resolution | journal = Journal of Molecular Biology | volume = 313 | issue = 5 | pages = 1045–57 | date = November 2001 | pmid = 11700061 | doi = 10.1006/jmbi.2001.5077 | url = https://zenodo.org/record/1229896 | access-date = 2019-09-09 | archive-date = 2021-01-22 | archive-url = https://web.archive.org/web/20210122161041/https://zenodo.org/record/1229896 | url-status = live }}</ref>]]
In [[eukaryote]]s, microtubules are long, hollow cylinders made up of polymerized [[Tubulin#Eukaryotic|α- and β-tubulin]] [[protein dimer|dimers]].<ref name="weisenberg">{{cite journal | vauthors = Weisenberg RC | title = Microtubule formation in vitro in solutions containing low calcium concentrations | journal = Science | volume = 177 | issue = 4054 | pages = 1104–5 | date = September 1972 | pmid = 4626639 | doi = 10.1126/science.177.4054.1104 | bibcode = 1972Sci...177.1104W | s2cid = 34875893 }}</ref> The inner space of the hollow microtubule cylinders is referred to as the lumen. The α and β-tubulin subunits are ~50% identical at the amino acid level, and both have a molecular weight of approximately 50 kDa.<ref name = "desai">{{cite journal | vauthors = Desai A, Mitchison TJ | title = Microtubule polymerization dynamics | journal = Annual Review of Cell and Developmental Biology | volume = 13 | pages = 83–117 | year = 1997 | pmid = 9442869 | doi = 10.1146/annurev.cellbio.13.1.83 }}</ref><ref>{{Cite journal |last1=Desai |first1=A. |last2=Mitchison |first2=T. J. |date=1997 |title=Microtubule polymerization dynamics |journal=Annual Review of Cell and Developmental Biology |volume=13 |pages=83–117 |doi=10.1146/annurev.cellbio.13.1.83 |issn=1081-0706 |pmid=9442869}}</ref>
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==Intracellular organization==
Microtubules are part of the [[cytoskeleton]], a structural network within the cell's [[cytoplasm]]. The roles of the microtubule cytoskeleton include mechanical support, organization of the cytoplasm, transport, motility and chromosome segregation. In developing neurons microtubules are known as [[neurotubule]]s,<ref name="Webster">{{cite web |title=Medical Definition of Neurotubules |url=https://www.merriam-webster.com/medical/neurotubules |website=www.merriam-webster.com |language=en |access-date=2018-09-26 |archive-date=2018-09-27 |archive-url=https://web.archive.org/web/20180927050133/https://www.merriam-webster.com/medical/neurotubules |url-status=live }}</ref> and they can modulate the dynamics of [[actin]], another component of the cytoskeleton.<ref>{{cite journal | vauthors = Zhao B, Meka DP, Scharrenberg R, König T, Schwanke B, Kobler O, Windhorst S, Kreutz MR, Mikhaylova M, Calderon de Anda F | title = Microtubules Modulate F-actin Dynamics during Neuronal Polarization | journal = Scientific Reports | volume = 7 | issue = 1 | page = 9583 | date = August 2017 | pmid = 28851982 | pmc = 5575062 | doi = 10.1038/s41598-017-09832-8 | bibcode = 2017NatSR...7.9583Z }}</ref> A microtubule is capable of growing and shrinking in order to generate force, and there are motor proteins that allow organelles and other cellular components to be carried along a microtubule. This combination of roles makes microtubules important for organizing and moving intracellular constituents.
The organization of microtubules in the cell is cell-type specific. In [[epithelia]], the minus-ends of the microtubule polymer are anchored near the site of cell-cell contact and organized along the apical-basal axis. After nucleation, the minus-ends are released and then re-anchored in the periphery by factors such as [[ninein]] and [[PLEKHA7]].<ref>{{cite journal | vauthors = Bartolini F, Gundersen GG | title = Generation of noncentrosomal microtubule arrays | journal = Journal of Cell Science | volume = 119 | issue = Pt 20 | pages = 4155–63 | date = October 2006 | pmid = 17038542 | doi = 10.1242/jcs.03227 | doi-access = free }}</ref> In this manner, they can facilitate the transport of proteins, vesicles and organelles along the apical-basal axis of the cell. In [[fibroblast]]s and other mesenchymal cell-types, microtubules are anchored at the centrosome and radiate with their plus-ends outwards towards the cell periphery (as shown in the first figure). In these cells, the microtubules play important roles in cell migration. Moreover, the polarity of microtubules is acted upon by motor proteins, which organize many components of the cell, including the [[endoplasmic reticulum]] and the [[Golgi apparatus]].
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===Polymerization===
Following the initial nucleation event, tubulin monomers must be added to the growing polymer. The process of adding or removing monomers depends on the concentration of αβ-tubulin dimers in solution in relation to the critical concentration, which is the steady state concentration of dimers at which there is no longer any net assembly or disassembly at the end of the microtubule. If the dimer concentration is greater than the critical concentration, the microtubule will polymerize and grow. If the concentration is less than the critical concentration, the length of the microtubule will decrease.<ref>{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P | title = Molecular Biology of the Cell. | edition = 4th | location = New York | publisher = Garland Science | date = 2002 | chapter = The Self-Assembly and Dynamic Structure of Cytoskeletal Filaments | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK26862/ | access-date = 2017-09-05 | archive-date = 2018-06-05 | archive-url = https://web.archive.org/web/20180605030647/https://www.ncbi.nlm.nih.gov/books/NBK26862/ | url-status = live }}</ref>
==Microtubule dynamics==
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==="Search and capture" model===
In 1986, [[Marc Kirschner]] and [[Tim Mitchison]] proposed that microtubules use their dynamic properties of growth and shrinkage at their plus ends to probe the three dimensional space of the cell. Plus ends that encounter kinetochores or sites of polarity become captured and no longer display growth or shrinkage. In contrast to normal dynamic microtubules, which have a half-life of 5–10 minutes, the captured microtubules can last for hours. This idea is commonly known as the "search and capture" model.<ref>{{cite journal | vauthors = Kirschner M, Mitchison T | title = Beyond self-assembly: from microtubules to morphogenesis | journal = Cell | volume = 45 | issue = 3 | pages = 329–42 | date = May 1986 | pmid = 3516413 | doi = 10.1016/0092-8674(86)90318-1 | s2cid = 36994346 }}</ref> Indeed, work since then has largely validated this idea. At the kinetochore, a variety of complexes have been shown to capture microtubule (+)-ends.<ref name="pmid18097444">{{cite journal | vauthors = Cheeseman IM, Desai A | title = Molecular architecture of the kinetochore-microtubule interface | journal = Nature Reviews. Molecular Cell Biology | volume = 9 | issue = 1 | pages = 33–46 | date = January 2008 | pmid = 18097444 | doi = 10.1038/nrm2310 | s2cid = 34121605 }}</ref> Moreover, a (+)-end capping activity for interphase microtubules has also been described.<ref name="pmid11058078">{{cite journal | vauthors = Infante AS, Stein MS, Zhai Y, Borisy GG, Gundersen GG | title = Detyrosinated (Glu) microtubules are stabilized by an ATP-sensitive plus-end cap | journal = Journal of Cell Science | volume = 113 | issue = 22 | pages = 3907–19 | date = November 2000 | doi = 10.1242/jcs.113.22.3907 | pmid = 11058078 | url = http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=11058078 | access-date = 2014-06-23 | archive-date = 2024-02-21 | archive-url = https://web.archive.org/web/20240221025058/https://journals.biologists.com/jcs/cgi/pmidlookup | url-status = live }}</ref> This later activity is mediated by [[formins]],<ref name="pmid11483957">{{cite journal | vauthors = Palazzo AF, Cook TA, Alberts AS, Gundersen GG | title = mDia mediates Rho-regulated formation and orientation of stable microtubules | journal = Nature Cell Biology | volume = 3 | issue = 8 | pages = 723–9 | date = August 2001 | pmid = 11483957 | doi = 10.1038/35087035 | s2cid = 7374170 }}</ref> the [[adenomatous polyposis coli]] protein, and [[MAPRE1|EB1]],<ref name="pmid15311282">{{cite journal | vauthors = Wen Y, Eng CH, Schmoranzer J, Cabrera-Poch N, Morris EJ, Chen M, Wallar BJ, Alberts AS, Gundersen GG | title = EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration | journal = Nature Cell Biology | volume = 6 | issue = 9 | pages = 820–30 | date = September 2004 | pmid = 15311282 | doi = 10.1038/ncb1160 | s2cid = 29214110 }}</ref> a protein that tracks along the growing plus ends of microtubules.
==Regulation of microtubule dynamics==
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==Proteins that interact with microtubules==
===Microtubule-associated proteins (
{{Main|Microtubule-associated protein}}
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=== Centrosomes ===
[[File:Centriole3D.png|thumb|298x298px|A 3D diagram of a centriole. Each circle represents one microtubule. In total there are 27 microtubules organized into 9 bundles of 3.]]
The [[centrosome]] is the main MTOC ([[microtubule organizing center]]) of the cell during mitosis. Each centrosome is made up of two cylinders called [[centriole]]s, oriented at right angles to each other. The centriole is formed from 9 main microtubules, each having two partial microtubules attached to it. Each centriole is approximately 400 nm long and around 200 nm in circumference.<ref name="pmid10209087">{{cite journal | vauthors = Marshall WF, Rosenbaum JL | title = Cell division: The renaissance of the centriole | journal = Current Biology | volume = 9 | issue = 6 | pages = R218–20 | date = March 1999 | pmid = 10209087 | doi = 10.1016/s0960-9822(99)80133-x| s2cid = 16951268 | doi-access = free | bibcode = 1999CBio....9.R218M }}</ref>
The centrosome is critical to mitosis as most microtubules involved in the process originate from the centrosome. The minus ends of each microtubule begin at the centrosome, while the plus ends radiate out in all directions. Thus the centrosome is also important in maintaining the polarity of microtubules during mitosis.<ref name="pmid9057082">{{cite journal | vauthors = Pereira G, Schiebel E | title = Centrosome-microtubule nucleation | journal = Journal of Cell Science | volume = 110 | issue = Pt 3 | pages = 295–300 | date = February 1997 | doi = 10.1242/jcs.110.3.295 | pmid = 9057082 }}</ref>
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