Editing Integrin (section)

=== Attachment of cell to the ECM ===
Integrins couple the cell-[[extracellular matrix]] (ECM) outside a cell to the [[cytoskeleton]] (in particular, the [[microfilament]]s) inside the cell. Which ligand in the ECM the integrin can bind to is defined by which α and β subunits the integrin is made of. Among the [[ligand]]s of integrins are [[fibronectin]], [[vitronectin]], [[collagen]], and [[laminin]]. The connection between the cell and the ECM may help the cell to endure pulling forces without being ripped out of the ECM. The ability of a cell to create this kind of bond is also of vital importance in [[ontogeny]].

Cell attachment to the ECM is a basic requirement to build a multicellular organism. Integrins are not simply hooks, but give the cell critical signals about the nature of its surroundings. Together with signals arising from receptors for soluble growth factors like [[Vascular endothelial growth factor|VEGF]], [[epidermal growth factor|EGF]], and many others, they enforce a cellular decision on what biological action to take, be it attachment, movement, death, or differentiation. Thus integrins lie at the heart of many cellular biological processes. The attachment of the cell takes place through formation of [[cell adhesion]] complexes, which consist of integrins and many cytoplasmic proteins, such as [[talin (protein)|talin]], [[vinculin]], [[paxillin]], and alpha-[[actinin]]. These act by regulating [[kinase]]s such as FAK ([[focal adhesion kinase]]) and [[Src kinase]] family members to phosphorylate substrates such as p130CAS thereby recruiting signaling adaptors such as [[CRK (gene)|CRK]]. These adhesion complexes attach to the actin cytoskeleton. The integrins thus serve to link two networks across the plasma membrane: the extracellular ECM and the intracellular actin filamentous system. Integrin α6β4 is an exception: it links to the keratin intermediate filament system in epithelial cells.<ref name="pmid16581764">{{cite journal | vauthors = Wilhelmsen K, Litjens SH, Sonnenberg A | title = Multiple functions of the integrin alpha6beta4 in epidermal homeostasis and tumorigenesis | journal = Molecular and Cellular Biology | volume = 26 | issue = 8 | pages = 2877–86 | date = April 2006 | pmid = 16581764 | pmc = 1446957 | doi = 10.1128/MCB.26.8.2877-2886.2006 }}</ref>

Focal adhesions are large molecular complexes, which are generated following interaction of integrins with ECM, then their clustering.  The clusters likely provide sufficient intracellular binding sites to permit the formation of stable signaling complexes on the cytoplasmic side of the cell membrane. So the focal adhesions contain integrin ligand, integrin molecule, and associate plaque proteins. Binding is propelled by changes in free energy.<ref name="pmid20805876">{{cite journal | vauthors = Olberding JE, Thouless MD, [[Ellen Arruda|Arruda EM]], Garikipati K | title = The non-equilibrium thermodynamics and kinetics of focal adhesion dynamics | journal = PLOS ONE | volume = 5 | issue = 8 | pages = e12043 | date = August 2010 | pmid = 20805876 | pmc = 2923603 | doi = 10.1371/journal.pone.0012043 | veditors = Buehler MJ | bibcode = 2010PLoSO...512043O | doi-access = free }}</ref> As previously stated, these complexes  connect the extracellular matrix to actin bundles. Cryo-electron tomography reveals that the adhesion contains particles on the cell membrane with diameter of 25 +/- 5&nbsp;nm and spaced at approximately 45&nbsp;nm.<ref name="pmid20694000">{{cite journal | vauthors = Patla I, Volberg T, Elad N, Hirschfeld-Warneken V, Grashoff C, Fässler R, Spatz JP, Geiger B, Medalia O | title = Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography | journal = Nature Cell Biology | volume = 12 | issue = 9 | pages = 909–15 | date = September 2010 | pmid = 20694000 | doi = 10.1038/ncb2095 | s2cid = 20775305 }}</ref> Treatment with Rho-kinase inhibitor [[Y-27632]] reduces the size of the particle, and it is extremely mechanosensitive.<ref name="urlMechanosensitive channels">{{cite web| url =http://www.ks.uiuc.edu/Research/MscLchannel/| title =Mechanosensitive channels| vauthors =Gullingsrud J, Sotomayor M| publisher =Theoretical and Computational Biophysics Group, Beckman Institute for Advanced Science and Technology: University of Illinois at Urbana-Champaign| url-status =live| archive-url =https://web.archive.org/web/20101202060530/http://www.ks.uiuc.edu/Research/MscLchannel/| archive-date =2010-12-02}}</ref>

One important function of integrins on cells in tissue culture is their role in [[cell migration]]. Cells adhere to a [[substrate (biology)|substrate]] through their integrins. During movement, the cell makes new attachments to the substrate at its front and concurrently releases those at its rear. When released from the substrate, integrin molecules are taken back into the cell by [[endocytosis]]; they are transported through the cell to its front by the [[endocytic cycle]], where they are added back to the surface. In this way they are cycled for reuse, enabling the cell to make fresh attachments at its leading front.<ref>{{cite journal | vauthors = Paul NR, Jacquemet G, Caswell PT | title = Endocytic Trafficking of Integrins in Cell Migration | language = en | journal = Current Biology | volume = 25 | issue = 22 | pages = R1092-105 | date = November 2015 | pmid = 26583903 | doi = 10.1016/j.cub.2015.09.049 | doi-access = free }}</ref> The cycle of integrin endocytosis and recycling back to the cell surface is important for migrating cells and also during animal development.<ref>{{cite journal | vauthors = Moreno-Layseca P, Icha J, Hamidi H, Ivaska J | title = Integrin trafficking in cells and tissues | journal = Nature Cell Biology | volume = 21 | issue = 2 | pages = 122–132 | date = February 2019 | pmid = 30602723 | pmc = 6597357 | doi = 10.1038/s41556-018-0223-z }}</ref>