Microtubule: Difference between revisions

{{short description|Polymer of tubulin that forms part of the cytoskeleton}}

 

 

Microtubules play an important role in a number of [[cellular processes]]. They are involved in maintaining the structure of the cell and, together with [[microfilament]]s and [[intermediate filament]]s, they form the cytoskeleton. They also make up the internal structure of [[cilia]] and [[flagella]]. They provide platforms for [[intracellular transport]] and are involved in a variety of cellular processes, including the movement of [[secretory]] [[Vesicle (biology and chemistry)|vesicles]], [[organelle]]s, and intracellular macromolecular assemblies.<ref>{{cite journal | vauthors = Vale RD | title = The molecular motor toolbox for intracellular transport | journal = Cell | volume = 112 | issue = 4 | pages = 467–80 | date = February 2003 | pmid = 12600311 | doi = 10.1016/S0092-8674(03)00111-9 | s2cid = 15100327 | doi-access = free }}</ref> They are also involved in cell division (by [[mitosis]] and [[meiosis]]) and are the main constituents of [[mitotic spindles]], which are used to pull eukaryotic [[chromosome]]s apart.

 

== History ==

 

 

== Structure ==

 

 

These α/β-tubulin [[protein dimer|dimers]] [[polymerize]] end-to-end into linear '''protofilaments''' that associate laterally to form a single microtubule, which can then be extended by the addition of more α/β-tubulin dimers. Typically, microtubules are formed by the parallel association of thirteen protofilaments, although microtubules composed of fewer or more protofilaments have been observed in various species&nbsp;<ref>{{cite journal | vauthors = Chaaban S, Brouhard GJ | title = A microtubule bestiary: structural diversity in tubulin polymers | journal = Molecular Biology of the Cell | volume = 28 | issue = 22 | pages = 2924–31 | date = 2017 | pmid = 29084910 | doi = 10.1091/mbc.E16-05-0271 | pmc = 5662251}}</ref> as well as ''in vitro''.<ref>{{cite journal | vauthors = Chrétien D, Metoz F, Verde F, Karsenti E, Wade RH | title = Lattice defects in microtubules: protofilament numbers vary within individual microtubules | journal = Journal of Cell Biology | volume = 117 | issue = 5 | pages = 1031–40 | date = June 1992 | pmid = 1577866 | doi = 10.1083/jcb.117.5.1031 | pmc = 2289483}}</ref>

Microtubules have a distinct polarity that is critical for their biological function. Tubulin polymerizes end to end, with the β-subunits of one tubulin dimer contacting the α-subunits of the next dimer. Therefore, in a protofilament, one end will have the α-subunits exposed while the other end will have the β-subunits exposed. These ends are designated the (−) and (+) ends, respectively. The protofilaments bundle parallel to one another with the same polarity, so, in a microtubule, there is one end, the (+) end, with only β-subunits exposed, while the other end, the (−) end, has only α-subunits exposed. While microtubule elongation can occur at both the (+) and (−) ends, it is significantly more rapid at the (+) end.<ref>{{cite journal | vauthors = Walker RA, O'Brien ET, Pryer NK, Soboeiro MF, Voter WA, Erickson HP, Salmon ED | title = Dynamic instability of individual microtubules analyzed by video light microscopy: rate constants and transition frequencies | journal = The Journal of Cell Biology | volume = 107 | issue = 4 | pages = 1437–48 | date = October 1988 | pmid = 3170635 | pmc = 2115242 | doi = 10.1083/jcb.107.4.1437 | citeseerx = 10.1.1.525.507 }}</ref>

 

 

The sequence and exact composition of molecules during microtubule formation can thus be summarised as follows: A β-tubulin connects in the context of a non-existent covalent bond with an α-tubulin, which in connected form are a heterodimer, since they consist of two different polypeptides (β-tubulin and α-tubulin). So after the heterodimers are formed, they join together to form long chains that rise figuratively in one direction (e.g. upwards). These heterodimers, which are connected in a certain direction, form protofilaments. These long chains (protofilaments) now gradually accumulate next to each other so that a tube-like structure is formed, which has a lumen typical of a tube. Accordingly, mostly 13 protofilaments form the outer wall of the microtubules. The heterodimers consist of a positive and negative end, with alpha-tubulin forming the negative end and beta-tubulin the positive end. Due to the fact that the heterodimers are stacked on top of each other, there is always a negative and positive end. Microtubules grow by an addition of heterodimers at the plus end.

 

 

==Intracellular organization==

 

 

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]].

===Polymerization===

 

 

==Microtubule dynamics==

==="Search and capture" model===

 

 

==Regulation of microtubule dynamics==

* [[Detyrosination]]: the removal of the C-terminal [[tyrosine]] from alpha-tubulin. This reaction exposes a [[glutamate]] at the new C-terminus. As a result, microtubules that accumulate this modification are often referred to as Glu-microtubules. Although the tubulin carboxypeptidase has yet to be identified, the [[tubulin—tyrosine ligase]] (TTL) is known.<ref name="pmid8093886">{{cite journal | vauthors = Ersfeld K, Wehland J, Plessmann U, Dodemont H, Gerke V, Weber K | title = Characterization of the tubulin-tyrosine ligase | journal = The Journal of Cell Biology | volume = 120 | issue = 3 | pages = 725–32 | date = February 1993 | pmid = 8093886 | pmc = 2119537 | doi = 10.1083/jcb.120.3.725 }}</ref>

* Delta2: the removal of the last two residues from the C-terminus of alpha-tubulin.<ref name="pmid1931974">{{cite journal | vauthors = Paturle-Lafanechère L, Eddé B, Denoulet P, Van Dorsselaer A, Mazarguil H, Le Caer JP, Wehland J, Job D | title = Characterization of a major brain tubulin variant which cannot be tyrosinated | journal = Biochemistry | volume = 30 | issue = 43 | pages = 10523–8 | date = October 1991 | pmid = 1931974 | doi = 10.1021/bi00107a022 }}</ref> Unlike detyrosination, this reaction is thought to be irreversible and has only been documented in neurons.

* [[Polyglutamylation]]: the addition of a glutamate polymer (typically 4-6 residues long<ref name="pmid8104053">{{cite journal | vauthors = Audebert S, Desbruyères E, Gruszczynski C, Koulakoff A, Gros F, Denoulet P, Eddé B | title = Reversible polyglutamylation of alpha- and beta-tubulin and microtubule dynamics in mouse brain neurons | journal = Molecular Biology of the Cell | volume = 4 | issue = 6 | pages = 615–26 | date = June 1993 | pmid = 8104053 | pmc = 300968 | doi = 10.1091/mbc.4.6.615 }}</ref>) to the gamma-carboxyl group of any one of five glutamates found near the end of alpha-tubulin. Enzymes related to TTL add the initial branching glutamate (TTL4,5 and 7), while other enzymes that belong to the same family lengthen the polyglutamate chain (TTL6,11 and 13).<ref name="pmid22422711" />

* [[Polyglycylation]]: the addition of a glycine polymer (2-10 residues long) to the gamma-carboxyl group of any one of five glutamates found near the end of beta-tubulin. TTL3 and 8 add the initial branching glycine, while TTL10 lengthens the polyglycine chain.<ref name="pmid22422711" />

MAPs have been shown to play a crucial role in the regulation of microtubule dynamics ''in-vivo''. The rates of microtubule polymerization, depolymerization, and catastrophe vary depending on which [[microtubule-associated protein]]s (MAPs) are present. The originally identified MAPs from brain tissue can be classified into two groups based on their molecular weight. This first class comprises MAPs with a molecular weight below 55-62 kDa, and are called [[tau proteins|τ (tau) proteins]]. ''In-vitro'', tau proteins have been shown to directly bind microtubules, promote nucleation and prevent disassembly, and to induce the formation of parallel arrays.<ref>{{cite journal | vauthors = Mandelkow E, Mandelkow EM | title = Microtubules and microtubule-associated proteins | journal = Current Opinion in Cell Biology | volume = 7 | issue = 1 | pages = 72–81 | date = February 1995 | pmid = 7755992 | doi = 10.1016/0955-0674(95)80047-6 }}</ref> Additionally, tau proteins have also been shown to stabilize microtubules in axons and have been implicated in Alzheimer's disease.<ref>{{cite journal | vauthors = Bramblett GT, Goedert M, Jakes R, Merrick SE, Trojanowski JQ, Lee VM | title = Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding | journal = Neuron | volume = 10 | issue = 6 | pages = 1089–99 | date = June 1993 | pmid = 8318230 | doi = 10.1016/0896-6273(93)90057-X | s2cid = 23180847 }}</ref> The second class is composed of MAPs with a molecular weight of 200-1000 kDa, of which there are four known types: MAP-1, [[MAP2|MAP-2]], MAP-3 and [[MAP4|MAP-4]]. MAP-1 proteins consists of a set of three different proteins: [[MAP1A|A]], [[MAP1A|B]] and C. The C protein plays an important role in the retrograde transport of vesicles and is also known as [[Dynein#Cytoplasmic dynein|cytoplasmic dynein]]. MAP-2 proteins are located in the dendrites and in the body of neurons, where they bind with other cytoskeletal filaments. The MAP-4 proteins are found in the majority of cells and stabilize microtubules. In addition to MAPs that have a stabilizing effect on microtubule structure, other MAPs can have a destabilizing effect either by cleaving or by inducing depolymerization of microtubules. Three proteins called [[katanin]], [[spastin]], and fidgetin have been observed to regulate the number and length of microtubules via their destabilizing activities. Furthermore, [[CRACD-like protein]] is predicted to be localized to the microtubules.<ref>{{cite web |url= http://www.proteinatlas.org |title=The Human Protein Atlas|website=www.proteinatlas.org|access-date=2017-04-27|url-status=live|archive-url=https://web.archive.org/web/20170501045727/http://www.proteinatlas.org/|archive-date=2017-05-01}}</ref>

 

 

===Plus-end tracking proteins (+TIPs)===

=== 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 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>