Spectrin 2864344 221289670 2008-06-23T21:43:03Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. '''Spectrin''' is a [[cytoskeleton|cytoskeletal]] [[protein]] that lines the intracellular side of the [[plasma membrane]] of many cell types in pentagonal or hexagonal arrangements, forming a [[scaffolding]] and playing an important role in maintenance of [[plasma membrane]] integrity and cytoskeletal structure.<ref name="Huh">Huh GY, Glantz SB, Je S, Morrow JS, and Kim JH. (2001). Calpain proteolysis of alphaII-spectrin in the normal adult human brain. ''Neuroscience Letters''. '''316'''(1): 41-44. PMID 11720774. Retrieved on [[January 24]], [[2007]]. </ref> The hexagonal arrangements are formed by tetramers of spectrin associating with short [[actin]] filaments at either end of the tetramer. These short actin filaments act as junctional complexes allowing the formation of the hexagonal mesh. In certain types of brain injury such as [[diffuse axonal injury]], spectrin is irreversibly cleaved by the [[proteolysis|proteolytic]] [[enzyme]] [[calpain]], destroying the cytosketelon.<ref name="Büki">Büki A, Okonkwo DO, Wang KKW, and Povlishock JT. (2000). [http://www.jneurosci.org/cgi/content/abstract/20/8/2825 Cytochrome ''c'' Release and Caspase Activation in Traumatic Axonal Injury.] ''Journal of Neuroscience''. '''20'''(8): 2825-2834.PMID 10751434. Retrieved on [[January 24]], [[2007]].</ref> Spectrin cleavage causes the membrane to form [[bleb]]s and ultimately to be degraded, usually leading to the death of the cell.<ref name="Castillo and Babson">Castillo MR and Babson JR. (1998). Ca<sup>2+</sup>-dependent mechanisms of cell injury in cultured cortical neurons. ''Neuroscience''. '''86'''(4): 1133-1144. PMID 9697120. Retrieved on [[January 24]], [[2007]].</ref> == Spectrin in erythrocytes == The convenience of using [[erythrocyte]]s compared to other cell types means they have become the standard model for the investigation of the spectrin cytoskeleton. Dimeric spectrin is formed by the lateral association of αI and βI monomers to form a dimer, dimers then associate in a head-to-head formation to produce the tetramer. End-to-end association of these tetramers with short actin filaments produces the hexagonal complexes observed. Association with the intracellular face of the plasma membrane is by indirect interaction, through direct interactions with protein 4.1 and ankyrin, with [[transmembrane proteins]]. In animals, spectrin forms the meshwork that provides red blood cells their shape. The [[erythrocyte]] model demonstrates the importance of the spectrin cytoskeleton in that mutations in spectrin commonly cause hereditary defects of the erythrocyte, including [[hereditary elliptocytosis]] and [[hereditary spherocytosis]].<ref>{{cite journal | last = Delaunay | first =J | authorlink = | coauthors = | title =Genetic disorders of the red cell membranes | journal =FEBS Letters | volume =369 | issue =1 | pages =34–37 | publisher = | date =1995 | url = | doi = | pmid =7641880}} </ref> == Spectrin in invertebrates == There are three spectrins in invertebrates, α,β and β<sub>H</sub>. A mutation in β spectrin in ''[[C. elegans]]'' results in an uncoordinated [[phenotype]] in which the worms are paralysed and much shorter than [[wild-type]].<ref name="">{{cite journal | last =Hammarlund | first =M | authorlink = | coauthors =Davis WS, Jorgensen EM | title =Mutations in beta-spectrin disrupt axon outgrowth and sarcomere structure | journal =Journal of Cell Biology| volume =149 | issue =4|pages = 931–942 | publisher =The Rockefeller University Press | date = 2000 | url =http://www.jcb.org/cgi/content/full/149/4/931 | doi = | pmid =10811832 | accessdate =2007-02-11}} </ref> In addition to the morphological effects, the Unc-70 mutation also produce defective [[neurons]]. Neuron numbers are normal but neuronal outgrowth was defective. : Similarly, spectrin plays a role in ''[[Drosophila]]'' neurons. Knock-out of α or β spectrin in ''D. melanogastor'' results in neurons that are morphologically normal but have reduced [[neurotransmission]] at the [[neuromuscular junction]].<ref name="Featherstone ">{{cite journal | last =Featherstone | first =DE | authorlink = | coauthors =Davis WS, Dubreuil RR, Broadie K | title =Drosophila alpha- and beta-spectrin mutations disrupt presynaptic neurotransmitter release | journal =Journal of Neuroscience | volume =21 | issue =12 | pages =4215–4224 | publisher = | date =2001 | url =http://www.jneurosci.org/cgi/content/full/21/12/4215 | doi = | pmid =11404407 | accessdate =2007-02-11}} </ref> In animals, spectrin forms the meshwork that provides red blood cells their shape. == Spectrin in vertebrates == === Vertebrate spectrin genes === The spectrin gene family has undergone expansion during evolution. Rather than the one α and two β genes in invertebrates, there are two α spectrins (αI and αII) and five β spectrins (βI to V), named in the order of discovery. In humans, the genes are: * Alpha: {{Gene|SPTA1}}, {{Gene|SPTAN1}} * Beta: {{Gene|SPTB}}, {{Gene|SPTBN1}}, {{Gene|SPTBN2}}, {{Gene|SPTBN4}}, {{Gene|SPTBN5}} The production of spectrin is promoted by the [[transcription factor]] [[GATA1]]. === Role of spectrin in muscle tissue === Some evidence for the role of spectrins in muscle tissues exist. In [[myocardial cell]]s, αII spectrin distribution is co-incident with Z-discs and the plasma membrane of [[myofibrils]].<ref>{{cite journal | last =Bennett | first =PM | authorlink = | coauthors =Baines AJ, Lecomte MC, Maggs AM, Pinder JC | title = Not just a plasma membrane protein: in cardiac muscle cells alpha-II spectrin also shows a close association with myofibrils| journal =Journal of Muscle Research and Cell Motility | volume =25 | issue =2 | pages =119–126 | publisher = | date =2004 | url = | doi = | pmid =15360127}} </ref> Additionally, mice with an ankyrin (ankB) knock-out have disrupted calcium homeostasis in the myocardia. Affected mice have disrupted z-band and sarcomere morphology. In this experimental model ryanodine and IP<sub>3</sub> receptors have abnormal distribution in cultured myocytes. The [[calcium signaling]] of the cultured cells is disrupted. In humans, a mutation within the AnkB gene results in the [[long QT syndrome]] and sudden death, strengthening the evidence for a role for the spectrin cytoskeleton in excitable tissue. ==See also== *[[Spectrin repeat]] == References == {{Reflist|2}} {{Membrane proteins}} {{Cytoskeletal Proteins}} [[Category:Cytoskeleton]] [[ja:スペクトリン]]