cell cortex

File:Actin-cortex.png distribution in the cell cortex as shown by rhodamine phalloidin staining of HeLa cells that constitutively express Histone H2B-GFP to mark chromosomes. F-actin is thus red, while Histone H2B is displayed in green. The left-hand cell is in mitosis, as demonstrated by chromosome condensation, while the right-hand cell is in interphase (as determined by intact cell nucleus) in a suspended state. In both cases, F-actin is enriched around the cell periphery. Scale bar: 10 micrometers.]]

The cell cortex, also known as the actin cortex, cortical cytoskeleton or actomyosin cortex, is a specialized layer of cytoplasmic proteins on the inner face of the cell membrane. It functions as a modulator of membrane behavior and cell surface properties.{{cite journal | vauthors = Salbreux G, Charras G, Paluch E | title = Actin cortex mechanics and cellular morphogenesis | journal = Trends in Cell Biology | volume = 22 | issue = 10 | pages = 536–45 | date = October 2012 | pmid = 22871642 | doi = 10.1016/j.tcb.2012.07.001 }}{{cite journal | vauthors = Pesen D, Hoh JH | title = Micromechanical architecture of the endothelial cell cortex | journal = Biophysical Journal | volume = 88 | issue = 1 | pages = 670–9 | date = January 2005 | pmid = 15489304 | pmc = 1305044 | doi = 10.1529/biophysj.104.049965 | bibcode = 2005BpJ....88..670P }}{{cite book |first1=Bruce |last1=Alberts |first2=Alexander |last2=Johnson |first3=Julian |last3=Lewis |first4=Martin |last4=Raff |first5=Keith |last5=Roberts |first6=Peter |last6=Walter |chapter=Cross-linking Proteins with Distinct Properties Organize Different Assemblies of Actin Filaments |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK26809/#A3021 |title=Molecular Biology of the Cell |publisher=Garland Science |location=New York |year=2002 |isbn=0-8153-3218-1 |edition=4th |url=https://www.ncbi.nlm.nih.gov/books/NBK21054/}} In most eukaryotic cells lacking a cell wall, the cortex is an actin-rich network consisting of F-actin filaments, myosin motors, and actin-binding proteins.{{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 }}{{cite journal | vauthors = Clark AG, Wartlick O, Salbreux G, Paluch EK | title = Stresses at the cell surface during animal cell morphogenesis | journal = Current Biology | volume = 24 | issue = 10 | pages = R484-94 | date = May 2014 | pmid = 24845681 | doi = 10.1016/j.cub.2014.03.059 | doi-access = free | bibcode = 2014CBio...24.R484C }} The actomyosin cortex is attached to the cell membrane via membrane-anchoring proteins called ERM proteins that plays a central role in cell shape control.{{cite journal | vauthors = Fehon RG, McClatchey AI, Bretscher A | title = Organizing the cell cortex: the role of ERM proteins | journal = Nature Reviews. Molecular Cell Biology | volume = 11 | issue = 4 | pages = 276–87 | date = April 2010 | pmid = 20308985 | pmc = 2871950 | doi = 10.1038/nrm2866 }} The protein constituents of the cortex undergo rapid turnover, making the cortex both mechanically rigid and highly plastic, two properties essential to its function. In most cases, the cortex is in the range of 100 to 1000 nanometers thick.

In some animal cells, the protein spectrin may be present in the cortex. Spectrin helps to create a network by cross-linked actin filaments. The proportions of spectrin and actin vary with cell type.{{cite journal | vauthors = Machnicka B, Grochowalska R, Bogusławska DM, Sikorski AF, Lecomte MC | title = Spectrin-based skeleton as an actor in cell signaling | journal = Cellular and Molecular Life Sciences | volume = 69 | issue = 2 | pages = 191–201 | date = January 2012 | pmid = 21877118 | pmc = 3249148 | doi = 10.1007/s00018-011-0804-5 }} Spectrin proteins and actin microfilaments are attached to transmembrane proteins by attachment proteins between them and the transmembrane proteins. The cell cortex is attached to the inner cytosolic face of the plasma membrane in cells where the spectrin proteins and actin microfilaments form a mesh-like structure that is continuously remodeled by polymerization, depolymerization and branching.

Many proteins are involved in the cortex regulation and dynamics, including formins, with roles in actin polymerization, Arp2/3 complexes that give rise to actin branching and capping proteins. Due to the branching process and the density of the actin cortex, the cortical cytoskeleton can comprise a highly complex meshwork such as a fractal structure.{{cite journal | vauthors = Sadegh S, Higgins JL, Mannion PC, Tamkun MM, Krapf D | title = Plasma Membrane is Compartmentalized by a Self-Similar Cortical Actin Meshwork | journal = Physical Review X | volume = 7 | issue = 1 | date = 2017 | page = 011031 | pmid = 28690919 | pmc = 5500227 | doi = 10.1103/PhysRevX.7.011031 | arxiv = 1702.03997 | bibcode = 2017PhRvX...7a1031S }} Specialized cells are usually characterized by a very specific cortical actin cytoskeleton. For example, in red blood cells, the cell cortex consists of a two-dimensional cross-linked elastic network with pentagonal or hexagonal symmetry, tethered to the plasma membrane and formed primarily by spectrin, actin and ankyrin.{{cite journal | vauthors = Gov NS | title = Active elastic network: cytoskeleton of the red blood cell | journal = Physical Review E | volume = 75 | issue = 1 Pt 1 | pages = 011921 | date = January 2007 | pmid = 17358198 | doi = 10.1103/PhysRevE.75.011921 | bibcode = 2007PhRvE..75a1921G }} In neuronal axons, the actin or spectric cytoskeleton forms an array of periodic rings {{cite journal | vauthors = Xu K, Zhong G, Zhuang X | title = Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons | journal = Science | volume = 339 | issue = 6118 | pages = 452–6 | date = January 2013 | pmid = 23239625 | pmc = 3815867 | doi = 10.1126/science.1232251 | bibcode = 2013Sci...339..452X }} and in the sperm flagellum it forms a helical structure.{{cite journal | vauthors = Gervasi MG, Xu X, Carbajal-Gonzalez B, Buffone MG, Visconti PE, Krapf D | title = The actin cytoskeleton of the mouse sperm flagellum is organized in a helical structure | journal = Journal of Cell Science | volume = 131 | issue = 11 | pages = jcs215897 | date = June 2018 | pmid = 29739876 | pmc = 6031324 | doi = 10.1242/jcs.215897 }}

In plant cells, the cell cortex is reinforced by cortical microtubules underlying the plasma membrane. The direction of these cortical microtubules determines which way the cell elongates when it grows.

Functions

The cortex mainly functions to produce tension under the cell membrane, allowing the cell to change shape. This is primarily accomplished through myosin II motors, which pull on the filaments to generate stress. These changes in tension are required for the cell to change its shape as it undergoes cell migration and cell division.

In mitosis, F-actin and myosin II form a highly contractile and uniform cortex to drive mitotic cell rounding. The surface tension produced by the actomyosin cortex activity generates intracellular hydrostatic pressure capable of displacing surrounding objects to facilitate rounding.{{cite journal | vauthors = Stewart MP, Helenius J, Toyoda Y, Ramanathan SP, Muller DJ, Hyman AA | title = Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding | journal = Nature | volume = 469 | issue = 7329 | pages = 226–30 | date = January 2011 | pmid = 21196934 | doi = 10.1038/nature09642 | bibcode = 2011Natur.469..226S | s2cid = 4425308 }}{{cite journal | vauthors = Ramanathan SP, Helenius J, Stewart MP, Cattin CJ, Hyman AA, Muller DJ | title = Cdk1-dependent mitotic enrichment of cortical myosin II promotes cell rounding against confinement | journal = Nature Cell Biology | volume = 17 | issue = 2 | pages = 148–59 | date = February 2015 | pmid = 25621953 | doi = 10.1038/ncb3098 | s2cid = 5208968 }}

Thus, the cell cortex serves to protect the microtubule spindle from external mechanical disruption during mitosis.{{cite journal |last1=Lancaster |first1=O |title=Mitotic Rounding Alters Cell Geometry to Ensure Efficient Bipolar Spindle Formation |journal=Developmental Cell |date=2013 |volume=25 |issue=3 |pages=270–283 |doi=10.1016/j.devcel.2013.03.014 |pmid=23623611 |doi-access=free }} When external forces are applied at sufficiently large rate and magnitude to a mitotic cell, loss of cortical F-actin homogeneity occurs leading to herniation of blebs and a temporary loss of the ability to protect the mitotic spindle.{{cite journal |last1=Charras |first1=Guillaume |last2=Paluch |first2=Ewa |title=Blebs lead the way: how to migrate without lamellipodia |journal=Nature Reviews Molecular Cell Biology |date=September 2008 |volume=9 |issue=9 |pages=730–736 |doi=10.1038/nrm2453 |pmid=18628785 }}{{cite journal |last1=Cattin |first1=Cedric |title=Mechanical control of mitotic progression in single animal cells |journal=PNAS |date=2015 |volume=112 |issue=36 |pages=11258–11263 |doi=10.1073/pnas.1502029112 |pmid=26305930 |pmc=4568679 |bibcode=2015PNAS..11211258C |doi-access=free }} Genetic studies have shown that the cell cortex in mitosis is regulated by diverse genes such as Rhoa,{{cite journal |last1=Maddox |first1=A |title=RhoA is required for cortical retraction and rigidity during mitotic cell rounding |journal=J. Cell Biol. |date=2003 |volume=160 |issue=2 |pages=255–265 |doi=10.1083/jcb.200207130 |pmid=12538643 |s2cid=1491406 |doi-access=free |pmc=2172639 }} WDR1,{{cite journal |last1=Fujibuchi |first1=T |title=AIP1/WDR1 supports mitotic cell rounding |journal=Biochem. Biophys. Res. Commun. |date=2005 |volume=327 |issue=1 |pages=268–275 |doi=10.1016/j.bbrc.2004.11.156 |pmid=15629458 }} ERM proteins,{{cite journal |last1=Kunda |first1=P |title=Moesin Controls Cortical Rigidity, Cell Rounding, and Spindle Morphogenesis during Mitosis |journal=Current Biology |date=2008 |volume=18 |issue=2 |pages=91–101 |doi=10.1016/j.cub.2007.12.051 |pmid=18207738 |s2cid=831851 |doi-access=free |bibcode=2008CBio...18...91K }} Ect2,{{cite journal |last1=Matthews |first1=H |title=Changes in Ect2 Localization Couple Actomyosin-Dependent Cell Shape Changes to Mitotic Progression |journal=Developmental Cell |date=2013 |volume=23 |issue=2 |pages=371–383 |doi=10.1016/j.devcel.2012.06.003 |pmid=22898780 |pmc=3763371 |s2cid=1295956 |doi-access=free }} Pbl, Cdc42, {{not a typo|aPKC}}, Par6,{{cite journal |last1=Rosa |first1=A |title=Ect2/Pbl acts via Rho and polarity proteins to direct the assembly of an isotropic actomyosin cortex upon mitotic entry |journal=Developmental Cell |date=2015 |volume=32 |issue=5 |pages=604–616 |doi=10.1016/j.devcel.2015.01.012 |pmid=25703349 |s2cid=17482918 |doi-access=free |pmc=4359025 }} DJ-1 and FAM134A.{{cite journal |last1=Toyoda |first1=Y |title=Genome-scale single-cell mechanical phenotyping reveals disease-related genes involved in mitotic rounding |journal=Nature Communications |date=2017 |volume=8 |issue=1 |page=1266 |doi=10.1038/s41467-017-01147-6 |pmid=29097687 |pmc=5668354 |bibcode=2017NatCo...8.1266T |s2cid=19567646 |doi-access=free }}

In cytokinesis the cell cortex plays a central role by producing a myosin-rich contractile ring to constrict the dividing cell into two daughter cells.{{cite journal | vauthors = Green RA, Paluch E, Oegema K | title = Cytokinesis in animal cells | journal = Annual Review of Cell and Developmental Biology | volume = 28 | pages = 29–58 | date = November 2012 | pmid = 22804577 | doi = 10.1146/annurev-cellbio-101011-155718 }}

Cell cortex contractility is key for amoeboidal type cell migration characteristic of many cancer cell metastasis events.{{cite journal | vauthors = Olson MF, Sahai E | title = The actin cytoskeleton in cancer cell motility | journal = Clinical & Experimental Metastasis | volume = 26 | issue = 4 | pages = 273–87 | date = April 2009 | pmid = 18498004 | doi = 10.1007/s10585-008-9174-2 | doi-access = free }}

In addition to cell cortex also plays essential roles in the formation of tissues, organs and organisms. By pulling on adhesion complexes, the cortex promotes the expansion of contacts with other cells or with the extracellular matrix. Notably, during early mammalian development, the cortex pulls cells together to drive compaction and the formation of the morula.{{cite journal |last1=Maître |first1=Jean-Léon |last2=Niwayama |first2=Ritsuya |last3=Turlier |first3=Hervé |last4=Nédélec |first4=François |last5=Hiiragi |first5=Takashi |title=Pulsatile cell-autonomous contractility drives compaction in the mouse embryo |journal=Nature Cell Biology |date=July 2015 |volume=17 |issue=7 |pages=849–855 |doi=10.1038/ncb3185 |pmid=26075357 }}{{cite journal |last1=Firmin |first1=Julie |last2=Ecker |first2=Nicolas |last3=Rivet Danon |first3=Diane |last4=Özgüç |first4=Özge |last5=Barraud Lange |first5=Virginie |last6=Turlier |first6=Hervé |last7=Patrat |first7=Catherine |last8=Maître |first8=Jean-Léon |title=Mechanics of human embryo compaction |journal=Nature |date=16 May 2024 |volume=629 |issue=8012 |pages=646–651 |doi=10.1038/s41586-024-07351-x |pmid=38693259 |bibcode=2024Natur.629..646F }} Also, differences in cortical tension drives the sorting of the inner cell mass and trophectoderm progenitors during the formation of the morula,{{cite journal |last1=Maître |first1=Jean-Léon |last2=Turlier |first2=Hervé |last3=Illukkumbura |first3=Rukshala |last4=Eismann |first4=Björn |last5=Niwayama |first5=Ritsuya |last6=Nédélec |first6=François |last7=Hiiragi |first7=Takashi |title=Asymmetric division of contractile domains couples cell positioning and fate specification |journal=Nature |date=August 2016 |volume=536 |issue=7616 |pages=344–348 |doi=10.1038/nature18958 |pmid=27487217 |pmc=4998956 |bibcode=2016Natur.536..344M }} the sorting of germ layer progenitors during zebrafish gastrulation,{{cite journal |last1=Krieg |first1=M. |last2=Arboleda-Estudillo |first2=Y. |last3=Puech |first3=P.-H. |last4=Käfer |first4=J. |last5=Graner |first5=F. |last6=Müller |first6=D. J. |last7=Heisenberg |first7=C.-P. |title=Tensile forces govern germ-layer organization in zebrafish |journal=Nature Cell Biology |date=April 2008 |volume=10 |issue=4 |pages=429–436 |doi=10.1038/ncb1705 |pmid=18364700 }}{{cite journal |last1=Maître |first1=Jean-Léon |last2=Berthoumieux |first2=Hélène |last3=Krens |first3=Simon Frederik Gabriel |last4=Salbreux |first4=Guillaume |last5=Jülicher |first5=Frank |last6=Paluch |first6=Ewa |last7=Heisenberg |first7=Carl-Philipp |title=Adhesion Functions in Cell Sorting by Mechanically Coupling the Cortices of Adhering Cells |journal=Science |date=12 October 2012 |volume=338 |issue=6104 |pages=253–256 |doi=10.1126/science.1225399 |pmid=22923438 |bibcode=2012Sci...338..253M }} the invagination of the mesoderm and the elongation of the germ band elongation during drosophila gastrulation.{{cite journal |last1=Bertet |first1=Claire |last2=Sulak |first2=Lawrence |last3=Lecuit |first3=Thomas |title=Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation |journal=Nature |date=June 2004 |volume=429 |issue=6992 |pages=667–671 |doi=10.1038/nature02590 |pmid=15190355 |bibcode=2004Natur.429..667B }}{{cite journal |last1=Martin |first1=Adam C. |last2=Kaschube |first2=Matthias |last3=Wieschaus |first3=Eric F. |title=Pulsed contractions of an actin–myosin network drive apical constriction |journal=Nature |date=January 2009 |volume=457 |issue=7228 |pages=495–499 |doi=10.1038/nature07522 |pmid=19029882 |pmc=2822715 |bibcode=2009Natur.457..495M }}

Research

Basic research into the cell cortex is done with immortalised cell lines, typically HeLa cells, S2 cells, Normal rat kidney cells, and M2 cells.{{cite journal |vauthors=Chugh P, Paluch EK |title=The actin cortex at a glance |journal=J Cell Sci |volume=131 |issue=14 |pages= |date=July 2018 |pmid=30026344 |pmc=6080608 |doi=10.1242/jcs.186254 }} In M2 cells in particular, cellular blebs – which form without a cortex, then form one as they retract – are often used to model cortex formation and composition.

cell cortex

Functions

Research

References

Further reading