View source for Cell polarity

{{Short description|Polar morphology of a cell, a specific orientation of the cell structure}}
{{Other uses|Polarity (disambiguation){{!}}Polarity}}

'''Cell polarity''' refers to spatial differences in shape, structure, and function within a [[Cell (biology)|cell]]. Almost all cell types exhibit some form of polarity, which enables them to carry out specialized functions. Classical examples of polarized cells are described below, including epithelial cells with apical-basal polarity, [[neuron]]s in which signals propagate in one direction from [[dendrite]]s to [[axon]]s, and [[Cell migration|migrating cells]]. Furthermore, cell polarity is important during many types of [[asymmetric cell division]] to set up functional asymmetries between daughter cells.

Many of the key molecular players implicated in cell polarity are well conserved. For example, in [[metazoan]] cells, the {{not a typo|PAR-3/PAR-6/aPKC}} complex plays a fundamental role in cell polarity. While the biochemical details may vary, some of the core principles such as negative and/or positive feedback between different molecules are common and essential to many known polarity systems.<ref>{{Cite journal|last1=Altschuler|first1=Steven J.|last2=Angenent|first2=Sigurd B.|last3=Wang|first3=Yanqin|last4=Wu|first4=Lani F.|date=August 2008|title=On the spontaneous emergence of cell polarity|journal=Nature|volume=454|issue=7206|pages=886–889|doi=10.1038/nature07119|pmid=18704086|issn=1476-4687|pmc=2562338|bibcode=2008Natur.454..886A }}</ref>
[[File:Stauffen_Yu_etal.png|thumb|Polarized localization of [[Staufen (protein)|Staufen protein]] (white arrow) in ''Drosophila'' stage 9 oocyte (Stau:GFP, DAPI).]]

==Examples of polarized cells==

===Epithelial cells===
{{main|Epithelial polarity}}

Epithelial cells adhere to one another through [[tight junctions]], [[desmosome]]s and [[adherens junctions]], forming sheets of cells that line the surface of the animal body and internal cavities (e.g., digestive tract and circulatory system). These cells have an apical-basal polarity defined by the [[apical membrane]] facing the outside surface of the body, or the [[Lumen (anatomy)|lumen]] of internal cavities, and the [[basolateral membrane]] oriented away from the lumen. The basolateral membrane refers to both the lateral membrane where cell-cell junctions connect neighboring cells and to the basal membrane where cells are attached to the [[basement membrane]], a thin sheet of [[extracellular matrix]] proteins that separates the epithelial sheet from underlying cells and [[connective tissue]]. Epithelial cells also exhibit '''planar cell polarity''', in which specialized structures are orientated within the plane of the epithelial sheet. Some examples of planar cell polarity include the scales of fish being oriented in the same direction and similarly the feathers of birds, the fur of mammals, and the cuticular projections (sensory hairs, etc.) on the bodies and appendages of flies and other insects.<ref>{{cite journal|last=Wu|first=Jun|author2=Mlodzik, Marek A.|title=A quest for the mechanism regulating global planar cell polarity of tissues|journal=Trends in Cell Biology|date=29 June 2009|volume=19|issue=7|pages=295–305|doi=10.1016/j.tcb.2009.04.003|pmid=19560358|pmc=3501338}}</ref> Computational models have been suggested to simulate how a group of epithelial cells can form a variety of biological morphologies.<ref>{{cite thesis |type=PhD |last=Nissen |first=Silas Boye |date=2020 |title=Point Particles to Capture Polarized Embryonic Cells & Cold Pools in the Atmosphere |publisher=Niels Bohr Institute, Faculty of Science, University of Copenhagen |url=https://books.google.com/books?id=L9YoEAAAQBAJ}}</ref>

===Neurons===
{{main|Neuron}}
{{Further|Synapse}}

A neuron receives signals from neighboring cells through branched, cellular extensions called [[dendrites]]. The neuron then propagates an electrical signal down a specialized [[axon]] extension from the basal pole to the synapse, where neurotransmitters are released to propagate the signal to another neuron or effector cell (e.g., muscle or gland). The polarity of the neuron thus facilitates the directional flow of information, which is required for communication between neurons and effector cells.<ref>{{cite journal|last=Rasband|first=Matthew N.|title=The axon initial segment and the maintenance of neuronal polarity|journal=Nature Reviews Neuroscience|date=August 2010|pages=552–562|doi=10.1038/nrn2852|pmid=20631711|volume=11|issue=8|s2cid=23996233}}</ref>

===Migratory cells===
{{main|Cell migration}}

Many cell types are capable of migration, such as [[leukocytes]] and [[fibroblasts]], and in order for these cells to move in one direction, they must have a defined front and rear. At the front of the cell is the leading edge, which is often defined by a flat ruffling of the cell membrane called the [[lamellipodium]] or thin protrusions called [[filopodia]]. Here, [[actin]] polymerization in the direction of migration allows cells to extend the leading edge of the cell and to attach to the surface.<ref>{{cite journal|last=Ridley|first=Anne J.|author2=Schwartz, Martin A. |author3=Burridge, Keith |author4=Firtel, Richard A. |author5=Ginsberg, Mark H. |author6=Borisy, Gary |author7=Parsons, J. Thomas |author8= Horwitz, Alan Rick |title=Cell Migration: Integrating Signals from Front to back|journal=Science|date=5 December 2003|volume=302|issue=5651|pages=1704–1709|doi=10.1126/science.1092053|pmid=14657486|bibcode=2003Sci...302.1704R |s2cid=16029926|url=https://cdr.lib.unc.edu/record/uuid:dacf5b66-ae5e-47f0-96f5-3390867b9e12}}</ref> At the rear of the cell, adhesions are disassembled and bundles of actin [[microfilaments]], called [[stress fiber]]s, contract and pull the trailing edge forward to keep up with the rest of the cell. Without this front-rear polarity, cells would be unable to coordinate directed migration.<ref>{{cite journal|last=Friedl|first=Peter|author2=Wolf, Katarina|title=Tumour-cell invasion and migration: diversity and escape mechanisms|journal=Nature Reviews Cancer|date=May 2003|volume=3|pages=362–374|doi=10.1038/nrc1075|issue=5|pmid=12724734|s2cid=5547981}}</ref><ref>{{Cite journal |last1=Lin |first1=Yiyan |last2=Pal |first2=Dhiman Sankar |last3=Banerjee |first3=Parijat |last4=Banerjee |first4=Tatsat |last5=Qin |first5=Guanghui |last6=Deng |first6=Yu |last7=Borleis |first7=Jane |last8=Iglesias |first8=Pablo A. |last9=Devreotes |first9=Peter N. |date=2024-07-01 |title=Ras suppression potentiates rear actomyosin contractility-driven cell polarization and migration |url=https://www.nature.com/articles/s41556-024-01453-4 |journal=Nature Cell Biology |volume=26 |issue=7 |language=en |pages=1062–1076 |doi=10.1038/s41556-024-01453-4 |pmid=38951708 |pmc=11364469 |pmc-embargo-date=January 1, 2025 |issn=1476-4679}}</ref><ref>{{Cite journal |last1=Pal |first1=Dhiman Sankar |last2=Banerjee |first2=Tatsat |last3=Lin |first3=Yiyan |last4=de Trogoff |first4=Félix |last5=Borleis |first5=Jane |last6=Iglesias |first6=Pablo A. |last7=Devreotes |first7=Peter N. |date=July 2023 |title=Actuation of single downstream nodes in growth factor network steers immune cell migration |journal=Developmental Cell |language=en |volume=58 |issue=13 |pages=1170–1188.e7 |doi=10.1016/j.devcel.2023.04.019 |pmc=10524337 |pmid=37220748}}</ref>

=== Budding yeast ===
The budding yeast, ''[[Saccharomyces cerevisiae]]'', is a model system for eukaryotic biology in which many of the fundamental elements of polarity development have been elucidated. Yeast cells share many features of cell polarity with other organisms, but feature fewer protein components. In yeast, polarity is biased to form at an inherited landmark, a patch of the protein Rsr1 in the case of budding, or a patch of Rax1 in mating projections.<ref>{{Cite journal|last1=Vasen|first1=Gustavo|last2=Dunayevich|first2=Paula|last3=Colman-Lerner|first3=Alejandro|date=2020-05-09|title=Mitotic and pheromone-specific intrinsic polarization cues interfere with gradient sensing in Saccharomyces cerevisiae|journal=Proc Natl Acad Sci USA|volume=117|issue=12|pages=6580–6589|doi=10.1073/pnas.1912505117|pmid=32152126|pmc=7104260|doi-access=free|bibcode=2020PNAS..117.6580V }}</ref> In the absence of polarity landmarks (i.e. in gene deletion mutants), cells can perform spontaneous [[symmetry breaking]],<ref>{{Cite journal|last1=Wedlich-Soldner|first1=Roland|last2=Li|first2=Rong|date=2003-04-01|title=Spontaneous cell polarization: undermining determinism|journal=Nature Cell Biology|volume=5|issue=4|pages=267–270|doi=10.1038/ncb0403-267|pmid=12669070|s2cid=12408901}}</ref> in which the location of the polarity site is determined randomly. Spontaneous polarization still generates only a single bud site, which has been explained by positive feedback increasing polarity protein concentrations locally at the largest polarity patch while decreasing polarity proteins globally by depleting them. The master regulator of polarity in yeast is [[CDC42|Cdc42]], which is a member of the eukaryotic Ras-homologous [[Rho family of GTPases|Rho-family]] of GTPases, and a member of the super-family of small GTPases, which include Rop GTPases in plants and small GTPases in prokaryotes. For polarity sites to form, Cdc42 must be present and capable of cycling GTP, a process regulated by its [[guanine nucleotide exchange factor]] (GEF), Cdc24, and by its [[GTPase-activating proteins]] (GAPs). Cdc42 localization is further regulated by cell cycle queues, and a number of binding partners.<ref>{{Cite journal|last1=Irazoqui|first1=Javier E.|last2=Lew|first2=Daniel J.|date=2004-05-01|title=Polarity establishment in yeast|journal=Journal of Cell Science|volume=117|issue=11|pages=2169–2171|doi=10.1242/jcs.00953|pmid=15126618|issn=1477-9137|doi-access=}}</ref> A recent study to elucidate the connection between cell cycle timing and [[CDC42|Cdc42]] accumulation in the bud site uses [[optogenetics]] to control protein localization using light.<ref>{{Cite journal|last1=Witte|first1=Kristen|last2=Strickland|first2=Devin|last3=Glotzer|first3=Michael|date=2017-07-06|title=Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization|journal=eLife|volume=6|doi=10.7554/eLife.26722|issn=2050-084X|pmc=5536948|pmid=28682236 |doi-access=free }}</ref> During mating, these polarity sites can relocate. Mathematical modeling coupled with imaging experiments suggest the relocation is mediated by actin-driven vesicle delivery.<ref>{{Cite journal|last1=Savage|first1=Natasha S.|last2=Layton|first2=Anita T.|last3=Lew|first3=Daniel J.|date=2012-05-15|title=Mechanistic mathematical model of polarity in yeast|url=http://dx.doi.org/10.1091/mbc.e11-10-0837|journal=Molecular Biology of the Cell|volume=23|issue=10|pages=1998–2013|doi=10.1091/mbc.e11-10-0837|pmid=22438587|issn=1059-1524|pmc=3350562}}</ref><ref>{{Cite journal|last1=Ghose|first1=Debraj|last2=Lew|first2=Daniel|date=2020-05-01|title=Mechanistic insights into actin-driven polarity site movement in yeast|url=http://dx.doi.org/10.1091/mbc.e20-01-0040|journal=Molecular Biology of the Cell|volume=31|issue=10|pages=1085–1102|doi=10.1091/mbc.e20-01-0040|pmid=32186970|issn=1059-1524|pmc=7346724}}</ref>

==Vertebrate development==
{{see also|Embryogenesis|Embryonic development}}

The bodies of vertebrate animals are asymmetric along three axes: [[anterior and posterior|anterior-posterior]] (head to tail), [[dorsal-ventral]] (spine to belly), and left-right (for example, our heart is on the left side of our body). These polarities arise within the developing embryo through a combination of several processes: 1) [[asymmetric cell division]], in which two daughter cells receive different amounts of cellular material (e.g. mRNA, proteins), 2) asymmetric localization of specific proteins or RNAs within cells (which is often mediated by the cytoskeleton), 3) concentration gradients of secreted proteins across the embryo such as [[Wnt signaling pathway|Wnt]], [[NODAL|Nodal]], and [[Bone Morphogenic Proteins]] (BMPs), and 4) differential expression of membrane receptors and ligands that cause lateral inhibition, in which the receptor-expressing cell adopts one fate and its neighbors another.<ref>{{cite journal|last=Hashimoto|first=Masakazu|author2=Hamada, Hiroshi|title=Translation of anterior-posterior polarity into left-right polarity in the mouse embryo|journal=Current Opinion in Genetics & Development|date=August 2010|volume=20|issue=4|pages=433–437|doi=10.1016/j.gde.2010.04.002|pmid=20439159}}</ref><ref>{{cite journal|last=Johnston|first=Daniel St|author2=Ahringer, Julie|title=Cell Polarity in Eggs and Epithelia: Parallels and Diversity|journal=Cell|date=28 May 2010|volume=141|issue=5|pages=757–774|doi=10.1016/j.cell.2010.05.011|pmid=20510924|s2cid=13897324|doi-access=free}}</ref>

In addition to defining asymmetric axes in the adult organism, cell polarity also regulates both individual and collective cell movements during embryonic development such as [[apical constriction]], [[invagination]], and [[epiboly]]. These movements are critical for shaping the embryo and creating the complex structures of the adult body.

==Molecular basis==
Cell polarity arises primarily through the localization of specific proteins to specific areas of the cell membrane. This localization often requires both the recruitment of cytoplasmic proteins to the cell membrane and polarized [[vesicle transport]] along [[cytoskeletal]] filaments to deliver transmembrane proteins from the [[golgi apparatus]]. Many of the molecules responsible for regulating cell polarity are conserved across cell types and throughout metazoan species. Examples include the PAR complex ([[Cdc42]], PAR3/ASIP, PAR6, atypical [[protein kinase C]]),<ref>{{cite journal|vauthors=Izumi Y, Hirose T, Tamai Y, Hirai S, Nagashima Y, Fujimoto T, Tabuse Y, Kemphues KJ, Ohno S |title=An Atypical PKC Directly Associates and Colocalizes at the Epithelial Tight Junction with ASIP, a Mammalian Homologue of ''Caenorhabditis elegans'' Polarity Protein PAR-3|journal=J Cell Biol|volume=143|issue=1|pages=95–106|date=October 1998|pmid=9763423|pmc=2132825|doi=10.1083/jcb.143.1.95}}</ref><ref>{{cite journal|vauthors=Tabuse Y, Izumi Y, Piano F, Kemphues KJ, Miwa J, Ohno S |title=Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans|journal=Development|volume=125|issue=18|pages=3607–3614|date=September 1998|doi=10.1242/dev.125.18.3607|pmid=9716526}}</ref> Crumbs complex (Crb, PALS, PATJ, Lin7), and Scribble complex (Scrib, Dlg, Lgl).<ref>{{cite journal|author2-link=Keith E. Mostov|last=Bryant|first=David M.|author2=Mostov, Keith E.|title=From cells to organs: building polarized tissue|journal=Nature Reviews Molecular Cell Biology|date=November 2008|volume=9|pages=887–901|doi=10.1038/nrm2523|pmid=18946477|issue=11|pmc=2921794}}</ref>  These polarity complexes are localized at the cytoplasmic side of the cell membrane, asymmetrically within cells. For example, in epithelial cells the PAR and Crumbs complexes are localized along the apical membrane and the Scribble complex along the lateral membrane.<ref>{{cite journal|last=Johnston|first=Daniel St|author2=Ahringer, Julie|title=Cell Polarity in Eggs and Epithelia: Parallels and Diversity|journal=Cell|date=28 May 2010|volume=141|issue=5|pages=757–774|doi=10.1016/j.cell.2010.05.011|pmid=20510924|s2cid=13897324|doi-access=free}}</ref> Together with a group of signaling molecules called [[Rho family of GTPases|Rho GTPases]], these polarity complexes can regulate vesicle transport and also control the localization of cytoplasmic proteins primarily by regulating the phosphorylation of phospholipids called [[phosphoinositides]]. Phosphoinositides serve as docking sites for proteins at the cell membrane, and their state of phosphorylation determines which proteins can bind.<ref>{{cite journal|last=Orlando|first=Kelly|author2=Guo, Wei|title=Organization and Dynamics in Cell Polarity|journal=Cold Spring Harbor Perspectives in Biology|date=November 2009|volume=1|issue=5|doi=10.1101/cshperspect.a001321|pmid=20066116|page=a001321|pmc=2773647}}</ref>

== Polarity establishment ==
While many of the key polarity proteins are well conserved, different mechanisms exist to establish cell polarity in different cell types. Here, two main classes can be distinguished: (1) cells that are able to polarize spontaneously, and (2) cells that establish polarity based on intrinsic or environmental cues.<ref>{{Cite journal|last1=Wedlich-Soldner|first1=Roland|last2=Li|first2=Rong|date=2003-04-01|title=Spontaneous cell polarization: undermining determinism|journal=Nature Cell Biology|volume=5|issue=4|pages=267–270|doi=10.1038/ncb0403-267|pmid=12669070|s2cid=12408901}}</ref>

Spontaneous symmetry breaking can be explained by amplification of stochastic fluctuations of molecules due to non-linear chemical kinetics. The mathematical basis for this biological phenomenon was established by [[Alan Turing]] in his 1953 paper '[[The Chemical Basis of Morphogenesis|The chemical basis of morphogenesis]].'<ref>{{Cite journal|last1=Turing|first1=A. M.|last2=S|first2=F. R.|date=1952-08-14|title=The chemical basis of morphogenesis|journal=Phil. Trans. R. Soc. Lond. B|volume=237|issue=641|pages=37–72|doi=10.1098/rstb.1952.0012|issn=0080-4622|doi-access=|bibcode=1952RSPTB.237...37T }}</ref> While Turing initially attempted to explain pattern formation in a multicellular system, similar mechanisms can also be applied to intracellular pattern formation.<ref>{{Cite journal|last1=Gierer|first1=A.|last2=Meinhardt|first2=H.|date=1972-12-01|title=A theory of biological pattern formation|journal=Kybernetik|volume=12|issue=1|pages=30–39|doi=10.1007/BF00289234|pmid=4663624|s2cid=17746442|issn=0023-5946|url=https://edoc.bbaw.de/frontdoor/index/index/docId/160}}</ref> Briefly, if a network of at least two interacting chemicals (in this case, proteins) exhibits certain types of reaction kinetics, as well as differential diffusion, stochastic concentration fluctuations can give rise to the formation of large-scale stable patterns, thus bridging from a molecular length scale to a cellular or even tissue scale.

A prime example for the second type of polarity establishment, which relies on extracellular or intracellular cues, is the ''C. elegans'' zygote. Here, mutual inhibition between two sets of proteins guides polarity establishment and maintenance. On the one hand, PAR-3, PAR-6 and aPKC (called anterior PAR proteins) occupy both the plasma membrane and cytoplasm prior to symmetry breaking. PAR-1, the ''C. elegans''-specific ring-finger-containing protein PAR-2, and LGL-1 (called posterior PAR proteins) are present mostly in the cytoplasm.<ref>{{Cite web|url=http://www.wormbook.org/chapters/www_asymcelldiv/asymcelldiv.html|title=Asymmetric cell division and axis formation in the embryo|website=www.wormbook.org|access-date=2018-04-06}}</ref> The male centrosome provides a cue, which breaks an initially homogenous membrane distribution of anterior PARs by inducing cortical flows. These are thought to advect anterior PARs towards one side of the cell, allowing posterior PARs to bind to other pole (posterior).<ref>{{Cite journal|last1=Munro|first1=Edwin|last2=Nance|first2=Jeremy|last3=Priess|first3=James R.|date=2004-09-01|title=Cortical Flows Powered by Asymmetrical Contraction Transport PAR Proteins to Establish and Maintain Anterior-Posterior Polarity in the Early C. elegans Embryo|journal=Developmental Cell|language=en|volume=7|issue=3|pages=413–424|doi=10.1016/j.devcel.2004.08.001|pmid=15363415|issn=1534-5807|doi-access=free}}</ref><ref>{{Cite journal|last1=Goehring|first1=Nathan W.|last2=Trong|first2=Philipp Khuc|last3=Bois|first3=Justin S.|last4=Chowdhury|first4=Debanjan|last5=Nicola|first5=Ernesto M.|last6=Hyman|first6=Anthony A.|last7=Grill|first7=Stephan W.|date=2011-11-25|title=Polarization of PAR Proteins by Advective Triggering of a Pattern-Forming System|journal=Science|volume=334|issue=6059|pages=1137–1141|doi=10.1126/science.1208619|issn=0036-8075|pmid=22021673|hdl=10261/80314|s2cid=206535351|doi-access=free|bibcode=2011Sci...334.1137G }}</ref> Anterior and posterior PAR proteins then maintain polarity until cytokinesis by mutually excluding each other from their respective cell membrane areas.

==See also==
{{Portal|Biology}}
{{col div|colwidth=20em}}
*[[Epithelial polarity]]
*[[Cell migration]]
*[[Embryogenesis]]
*[[Embryonic development]]
*[[Asymmetric cell division]]
*[[3D cell culture]]
*[[Cell culture assay]]
*[[Madin-Darby canine kidney cells]]
{{colend}}

== References ==
{{Reflist|2}}

[[Category:Cell biology]]