Editing Cytoskeleton (section)

==Eukaryotic cytoskeleton==

[[Eukaryotic]] cells contain three main kinds of cytoskeletal filaments: [[microfilaments]], [[microtubules]], and [[intermediate filaments]]. In [[neuron]]s the intermediate filaments are known as [[neurofilament]]s.<ref name="Taran">{{cite journal |last1=Taran |first1=AS |last2=Shuvalova |first2=LD |last3=Lagarkova |first3=MA |last4=Alieva |first4=IB |title=Huntington's Disease-An Outlook on the Interplay of the HTT Protein, Microtubules and Actin Cytoskeletal Components. |journal=Cells |date=22 June 2020 |volume=9 |issue=6 |page=1514 |doi=10.3390/cells9061514 |pmid=32580314|pmc=7348758 |doi-access=free }}</ref>  Each type is formed by the [[polymerization]] of a distinct type of [[protein subunit]] and has its own characteristic shape and [[intracellular]] distribution. Microfilaments are [[polymer]]s of the protein [[actin]] and are 7&nbsp;nm in diameter. Microtubules are composed of [[tubulin]] and are 25&nbsp;nm in diameter. Intermediate filaments are composed of various proteins, depending on the type of  cell in which they are found; they are normally 8-12&nbsp;nm in diameter.<ref name="Hardin"/>  The cytoskeleton provides the cell with structure and shape, and by [[excluded volume|excluding]] [[macromolecules]] from some of the [[cytosol]], it adds to the level of [[macromolecular crowding]] in this compartment.<ref>{{cite journal | vauthors = Minton AP | title = Confinement as a determinant of macromolecular structure and reactivity | journal = Biophysical Journal | volume = 63 | issue = 4 | pages = 1090–100 | date = October 1992 | pmid = 1420928 | pmc = 1262248 | doi = 10.1016/S0006-3495(92)81663-6 | bibcode = 1992BpJ....63.1090M }}</ref> Cytoskeletal elements interact extensively and intimately with cellular membranes.<ref>{{cite journal | vauthors = Doherty GJ, McMahon HT | s2cid = 17352662 | title = Mediation, modulation, and consequences of membrane-cytoskeleton interactions | journal = Annual Review of Biophysics | volume = 37 | pages = 65–95 | year = 2008 | pmid = 18573073 | doi = 10.1146/annurev.biophys.37.032807.125912 }}</ref>

Research into [[Neurodegeneration|neurodegenerative disorders]] such as [[Parkinson's disease]], [[Alzheimer's disease]], [[Huntington's disease]], and [[amyotrophic lateral sclerosis]] (ALS) indicate that the cytoskeleton is affected in these diseases.<ref name="PelucchiStringhi2020">{{cite journal|last1=Pelucchi|first1=Silvia|last2=Stringhi|first2=Ramona|last3=Marcello|first3=Elena|title=Dendritic Spines in Alzheimer's Disease: How the Actin Cytoskeleton Contributes to Synaptic Failure|journal=International Journal of Molecular Sciences|volume=21|issue=3|year=2020|pages=908|issn=1422-0067|doi=10.3390/ijms21030908|pmid=32019166|pmc=7036943|doi-access=free}}</ref> Parkinson's disease is marked by the degradation of neurons, resulting in tremors, rigidity, and other non-motor symptoms. Research has shown that microtubule assembly and stability in the cytoskeleton is compromised causing the neurons to degrade over time.<ref>{{cite journal | vauthors = Pellegrini L, Wetzel A, Grannó S, Heaton G, Harvey K | title = Back to the tubule: microtubule dynamics in Parkinson's disease | journal = Cellular and Molecular Life Sciences | volume = 74 | issue = 3 | pages = 409–434 | date = February 2017 | pmid = 27600680 | pmc = 5241350 | doi = 10.1007/s00018-016-2351-6 }}</ref> In Alzheimer's disease, [[tau protein]]s which stabilize microtubules malfunction in the progression of the illness causing pathology of the cytoskeleton.<ref>{{cite journal | vauthors = Bamburg JR, Bloom GS | title = Cytoskeletal pathologies of Alzheimer's Disease | journal = Cell Motility and the Cytoskeleton | volume = 66 | issue = 8 | pages = 635–49 | date = August 2009 | pmid = 19479823 | pmc = 2754410 | doi = 10.1002/cm.20388 }}</ref> Excess glutamine in the Huntington protein involved with linking vesicles onto the cytoskeleton is also proposed to be a factor in the development of Huntington's Disease.<ref>{{cite journal | vauthors = Caviston JP, Holzbaur EL | title = Huntingtin protein is an essential integrator of intracellular vesicular trafficking | journal = Trends in Cell Biology | volume = 19 | issue = 4 | pages = 147–55 | date = April 2009 | pmid = 19269181 | pmc = 2930405 | doi = 10.1016/j.tcb.2009.01.005 }}</ref> Amyotrophic lateral sclerosis results in a loss of movement caused by the degradation of motor neurons, and also involves defects of the cytoskeleton.<ref>{{cite book | vauthors = Julien JP, Millecamps S, Kriz J | chapter = Cytoskeletal Defects in Amyotrophic Lateral Sclerosis (Motor Neuron Disease) | title = Nuclear Organization in Development and Disease | journal = Novartis Foundation Symposium | series = Novartis Foundation Symposia | volume = 264 | pages = 183–92; discussion 192–6, 227–30 | date = 2005 | doi = 10.1002/0470093765.ch12 | pmid = 15773754 | isbn = 978-0-470-09373-3 }}</ref>

[[Stuart Hameroff]] and [[Roger Penrose]] suggest a role of microtubule vibrations in [[neurons]] in the origin of [[consciousness]].<ref>{{Cite web|url=https://www.elsevier.com/about/press-releases/research-and-journals/discovery-of-quantum-vibrations-in-microtubules-inside-brain-neurons-corroborates-controversial-20-year-old-theory-of-consciousness|title=Discovery of Quantum Vibrations in "Microtubules" Inside Brain Neurons Corroborates Controversial 20-Year-Old Theory of Consciousness|last=Elsevier|website=www.elsevier.com|language=en|access-date=2017-11-20|url-status=live|archive-url=https://web.archive.org/web/20161107154319/https://www.elsevier.com/about/press-releases/research-and-journals/discovery-of-quantum-vibrations-in-microtubules-inside-brain-neurons-corroborates-controversial-20-year-old-theory-of-consciousness|archive-date=2016-11-07}}</ref><ref>{{cite journal |last1=Hameroff |first1=Stuart |last2=Penrose |first2=Roger |title=Consciousness in the universe |journal=Physics of Life Reviews |date=March 2014 |volume=11 |issue=1 |pages=39–78 |doi=10.1016/j.plrev.2013.08.002|pmid=24070914 |doi-access=free }}</ref>

Accessory proteins including [[motor protein]]s regulate and link the filaments to other cell compounds and each other and are essential for controlled assembly of cytoskeletal filaments in particular locations.<ref>{{Cite book|title=Molecular Biology of the Cell|last=Alberts|first=Bruce|publisher=Garland Science|year=2015|isbn=978-0-8153-4464-3|pages=889}}</ref>

A number of small-molecule [[cytoskeletal drugs]] have been discovered that interact with actin and microtubules. These compounds have proven useful in studying the cytoskeleton, and several have clinical applications.

===Microfilaments===
{{main|Microfilament}}
{{Multiple image
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| image1 = Microfilament Structure.svg
| caption1 = Structure of a [[microfilament]]
| image2 = MEF microfilaments.jpg
| caption2 = Actin cytoskeleton of [[mus musculus|mouse]] [[embryo]] [[fibroblast]]s, stained with [[phalloidin]]
}}

Microfilaments, also known as actin filaments, are composed of linear polymers of [[Actin#G-Actin|G-actin]] proteins, and generate force when the growing (plus) end of the filament pushes against a barrier, such as the cell membrane. They also act as tracks for the movement of [[myosin]] molecules that affix to the microfilament and "walk" along them. In general, the major component or protein of microfilaments are actin. The G-actin monomer combines to form a polymer which continues to form the microfilament (actin filament). These subunits then assemble into two chains that intertwine into what are called [[Actin#F-Actin|F-actin]] chains.<ref name="Cooper 2000">{{Cite journal|last=Cooper|first=Geoffrey M.|date=2000|title=Structure and Organization of Actin Filaments|url=https://www.ncbi.nlm.nih.gov/books/NBK9908/|journal=The Cell: A Molecular Approach. 2nd Edition|language=en|url-status=live|archive-url=https://web.archive.org/web/20180502014625/https://www.ncbi.nlm.nih.gov/books/NBK9908/|archive-date=2018-05-02}}</ref> Myosin motoring along F-actin filaments generates contractile forces in so-called actomyosin fibers, both in muscle as well as most non-muscle cell types.<ref name=gunning>{{cite journal | vauthors = Gunning PW, Ghoshdastider U, Whitaker S, Popp D, Robinson RC | title = The evolution of compositionally and functionally distinct actin filaments | journal = Journal of Cell Science | volume = 128 | issue = 11 | pages = 2009–19 | date = June 2015 | pmid = 25788699 | doi = 10.1242/jcs.165563 | doi-access = free }}</ref> Actin structures are controlled by the [[Rho family]] of small GTP-binding proteins such as Rho itself for contractile acto-myosin filaments ("stress fibers"), Rac for lamellipodia and Cdc42 for filopodia.

Functions include:
* [[Muscle contraction]]
* Cell movement
* Intracellular transport/trafficking
* Maintenance of [[Eukaryote|eukaryotic]] cell shape
* [[Cytokinesis]]
* Cytoplasmic streaming<ref name="Cooper 2000"/>

===Intermediate filaments===
{{main|Intermediate filament}}
{{Multiple image
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| image1 = Intermediate filaments.svg
| caption1 = Structure of an [[intermediate filament]]
| image2 = KeratinF9.png
| caption2 = Microscopy of [[keratin]] filaments inside cells
}}

Intermediate filaments are a part of the cytoskeleton of many [[Eukaryote|eukaryotic]] cells. These filaments, averaging 10 nanometers in diameter, are more stable (strongly bound) than microfilaments, and heterogeneous constituents of the cytoskeleton. Like [[actin]] filaments, they function in the maintenance of cell-shape by bearing tension ([[microtubules]], by contrast, resist compression but can also bear tension during [[mitosis]] and during the positioning of the centrosome). Intermediate filaments organize the internal tridimensional structure of the cell, anchoring [[organelle]]s and serving as structural components of the [[nuclear lamina]]. They also participate in some cell-cell and cell-matrix junctions. [[Nuclear lamina]] exist in all animals and all tissues. Some animals like the [[drosophila melanogaster|fruit fly]] do not have any cytoplasmic intermediate filaments. In those animals that express cytoplasmic intermediate filaments, these are tissue specific.<ref name="Herrmann">{{cite journal | vauthors = Herrmann H, Bär H, Kreplak L, Strelkov SV, Aebi U | title = Intermediate filaments: from cell architecture to nanomechanics | journal = Nature Reviews. Molecular Cell Biology | volume = 8 | issue = 7 | pages = 562–73 | date = July 2007 | pmid = 17551517 | doi = 10.1038/nrm2197 | s2cid = 27115011 }}</ref> [[Keratin]] intermediate filaments in [[epithelial]] cells provide protection for different mechanical stresses the skin may endure. They also provide protection for organs against metabolic, oxidative, and chemical stresses. Strengthening of epithelial cells with these intermediate filaments may prevent onset of [[apoptosis]], or cell death, by reducing the probability of stress.<ref>{{cite journal | vauthors = Pan X, Hobbs RP, Coulombe PA | title = The expanding significance of keratin intermediate filaments in normal and diseased epithelia | journal = Current Opinion in Cell Biology | volume = 25 | issue = 1 | pages = 47–56 | date = February 2013 | pmid = 23270662 | pmc = 3578078 | doi = 10.1016/j.ceb.2012.10.018 }}</ref>

Intermediate filaments are most commonly known as the support system or "scaffolding" for the cell and nucleus while also playing a role in some cell functions. In combination with proteins and [[desmosome]]s, the intermediate filaments form cell-cell connections and anchor the cell-matrix junctions that are used in messaging between cells as well as vital functions of the cell. These connections allow the cell to communicate through the desmosome of multiple cells to adjust structures of the tissue based on signals from the cells environment. Mutations in the IF proteins have been shown to cause serious medical issues such as premature aging, desmin mutations compromising organs, [[Alexander disease|Alexander Disease]], and [[muscular dystrophy]].<ref name="Herrmann"/>

Different intermediate filaments are:
* made of [[vimentin]]s. Vimentin intermediate filaments are in general present in mesenchymal cells.
* made of [[keratin]]. Keratin is present in general in epithelial cells.
* [[neurofilament]]s of neural cells.
* made of [[lamin]], giving structural support to the nuclear envelope.
* made of [[desmin]], play an important role in structural and mechanical support of muscle cells.<ref>{{cite journal | vauthors = Paulin D, Li Z | title = Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle | journal = Experimental Cell Research | volume = 301 | issue = 1 | pages = 1–7 | date = November 2004 | pmid = 15501438 | doi = 10.1016/j.yexcr.2004.08.004 }}</ref>

===Microtubules===
{{main|Microtubule}}
{{Multiple image
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| image1 = Microtubule Structure.svg
| caption1 = Structure of a [[microtubule]]
| image2 = Btub.jpg
| caption2 = Microtubules in a gel-fixated cell
}}

Microtubules are hollow cylinders about 23&nbsp;nm in diameter (lumen diameter of approximately 15&nbsp;nm), most commonly comprising 13 [[Microtubule|protofilaments]] that, in turn, are polymers of alpha and beta [[tubulin]]. They have a very dynamic behavior, binding [[Guanosine triphosphate|GTP]] for polymerization. They are commonly organized by the [[centrosome]].

In nine triplet sets (star-shaped), they form the [[centrioles]], and in nine doublets oriented about two additional microtubules (wheel-shaped), they form cilia and flagella. The latter formation is commonly referred to as a "9+2" arrangement, wherein each doublet is connected to another by the protein [[dynein]]. As both flagella and cilia are structural components of the cell, and are maintained by microtubules, they can be considered part of the cytoskeleton. There are two types of cilia:&nbsp;motile&nbsp;and&nbsp;non-motile cilia. Cilia are short and more numerous than flagella. The motile cilia have a rhythmic waving or beating motion compared to the non-motile cilia which receive sensory information for the cell; processing signals from the other cells or the fluids surrounding it. Additionally, the microtubules control the beating (movement) of the cilia and flagella.<ref name="auto">{{cite journal |url=https://www.ncbi.nlm.nih.gov/books/NBK21698/| title=Cilia and Flagella: Structure and Movement |first1=Harvey |last1=Lodish |first2=Arnold |last2=Berk |first3=S. Lawrence |last3=Zipursky |first4=Paul |last4=Matsudaira |first5=David |last5=Baltimore |first6=James |last6=Darnell |date=2 May 2018 |access-date=2 May 2018|via=www.ncbi.nlm.nih.gov|url-status=live|archive-url= https://web.archive.org/web/20180502014625/https://www.ncbi.nlm.nih.gov/books/NBK21698/ |archive-date=2 May 2018}}</ref> Also, the dynein arms attached to the microtubules function as the molecular motors. The motion of the cilia and flagella is created by the microtubules sliding past one another, which requires ATP.<ref name="auto"/>
They play key roles in:
* intracellular transport (associated with dyneins and [[kinesin]]s, they transport [[organelles]] like [[mitochondria]] or [[vesicle (biology)|vesicles]]).
* [[File:Bronchiolar area cilia cross-sections 2.jpg|thumb|Cross section diagram through the&nbsp;cilium,&nbsp;showing the “9 + 2” arrangement of microtubules]]the [[axoneme]] of [[cilium|cilia]] and [[flagellum|flagella]].
* the [[mitotic spindle]].
* synthesis of the cell wall in plants.

In addition to the roles described above, Stuart Hameroff and Roger Penrose have proposed that microtubules function in consciousness.<ref>Hameroff, S. and Penrose, R. Physics of Life Reviews 2014, 11, 39-78</ref>

===Comparison===
{| class=wikitable
|-
! Cytoskeleton <br/>type<ref name=boron25Unless>Unless else specified in boxes, then ref is:{{cite book | first = Walter F. | last = Boron | name-list-style = vanc |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |year=2003 |page=1300 |isbn=978-1-4160-2328-9 }} Page 25</ref>
! Diameter <br/>([[nanometre|nm]])<ref>{{cite journal | vauthors = Fuchs E, Cleveland DW | title = A structural scaffolding of intermediate filaments in health and disease | journal = Science | volume = 279 | issue = 5350 | pages = 514–9 | date = January 1998 | pmid = 9438837 | doi = 10.1126/science.279.5350.514 | bibcode = 1998Sci...279..514F }}</ref>
! Structure
! Subunit examples<ref name=boron25Unless/>
|-
! [[Microfilaments]]
| 6
| [[Double helix]]
| [[Actin]]
|-
! [[Intermediate filament|Intermediate <br/>filament]]s
| 10
| Two anti-parallel [[helix|helices]]/dimers, forming tetramers
|
* [[Vimentin]] ([[mesenchyme]])
* [[Glial fibrillary acidic protein]] ([[glial cell]]s)
* [[Neurofilament]] proteins (neuronal processes)
* [[Keratin]]s ([[epithelial cell]]s)
* [[Nuclear lamins]]
|-
! [[Microtubule]]s
| 23
| [[Protofilament]]s, in turn consisting of tubulin subunits in complex with [[Stathmin protein domain|stathmin]]<ref name="pmid17029844">{{cite journal | vauthors = Steinmetz MO | title = Structure and thermodynamics of the tubulin-stathmin interaction | journal = Journal of Structural Biology | volume = 158 | issue = 2 | pages = 137–47 | date = May 2007 | pmid = 17029844 | doi = 10.1016/j.jsb.2006.07.018 }}</ref>
| [[α-bubulin|α-]] and [[β-tubulin|β-Tubulin]]
|}

===Septins===
{{main|Septin}}

Septins are a group of the highly conserved [[Guanosine triphosphate|GTP]] binding proteins found in [[eukaryotes]]. Different septins form [[protein complex]]es with each other. These can assemble to filaments and rings. Therefore, septins can be considered part of the cytoskeleton.<ref name="Mostowy2012">{{cite journal | vauthors = Mostowy S, Cossart P | title = Septins: the fourth component of the cytoskeleton | journal = Nature Reviews. Molecular Cell Biology | volume = 13 | issue = 3 | pages = 183–94 | date = February 2012 | pmid = 22314400 | doi = 10.1038/nrm3284 | s2cid = 2418522 }}</ref> The function of septins in cells include serving as a localized attachment site for other [[protein]]s, and preventing the [[diffusion]] of certain molecules from one cell compartment to another.<ref name="Mostowy2012"/> In yeast cells, they build scaffolding to provide structural support during cell division and compartmentalize parts of the cell. Recent research in human cells suggests that septins build cages around bacterial pathogens, immobilizing the harmful microbes and preventing them from invading other cells.<ref name=Mascarelli_2011>{{cite journal | vauthors = Mascarelli A | title = Septin proteins take bacterial prisoners: A cellular defence against microbial pathogens holds therapeutic potential | journal = Nature |date=December 2011 | doi = 10.1038/nature.2011.9540 | s2cid = 85080734 | doi-access = free }}</ref>

===Spectrin===
{{main|Spectrin}}

Spectrin is a cytoskeletal [[protein]] that lines the intracellular side of the [[plasma membrane]] in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a [[scaffolding]] and playing an important role in maintenance of [[plasma membrane]] integrity and cytoskeletal structure.<ref name="Huh">{{cite journal | vauthors = Huh GY, Glantz SB, Je S, Morrow JS, Kim JH | title = Calpain proteolysis of alpha II-spectrin in the normal adult human brain | journal = Neuroscience Letters | volume = 316 | issue = 1 | pages = 41–4 | date = December 2001 | pmid = 11720774 | doi = 10.1016/S0304-3940(01)02371-0 | s2cid = 53270680 }}</ref>

===Yeast cytoskeleton===
{{see also | Yeast}}

In budding [[yeast]] (an important [[model organism]]), [[actin]] forms cortical patches, actin cables, and a cytokinetic ring and the cap. Cortical patches are discrete actin bodies on the membrane and are vital for [[endocytosis]], especially the recycling of glucan synthase which is important for [[cell wall]] synthesis. Actin cables are bundles of [[actin filaments]] and are involved in the transport of [[vesicle (biology and chemistry)|vesicles]] towards the cap (which contains a number of different proteins to polarize cell growth) and in the positioning of mitochondria. The [[cytokinesis|cytokinetic]] ring forms and constricts around the site of [[cell division]].<ref name="Pruyne2000">{{cite journal | vauthors = Pruyne D, Bretscher A | title = Polarization of cell growth in yeast | journal = Journal of Cell Science | volume = 113 ( Pt 4) | issue = 4 | pages = 571–85 | date = February 2000 | doi = 10.1242/jcs.113.4.571 | pmid = 10652251 | doi-access = free }}</ref>