View source for Spectrin

{{Short description|Cytoskeletal protein}}
[[Image:Cytoskeleton (Elliptocytosis).png|thumb|300px|A schematic diagram of spectrin and other cytoskeletal molecules]]

[[File:Spectrin localization under the neuronal plasme membrane..jpg|thumb|300px|Localization of alpha-II spectrin in green under the plasma membrane of rat neurons in tissue culture as shown with [[confocal microscopy]] and [[immunofluorescence]]. The nuclei of the cells is revealed in blue by the DNA dye [[DAPI]].]]

'''Spectrin''' is a [[cytoskeleton|cytoskeletal]] [[protein]] that lines the intracellular side of the [[plasma membrane]] in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a [[scaffolding|scaffold]] and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure.<ref name="Huh">{{cite journal | pmid = 11720774 | volume=316 | issue=1 | title=Calpain proteolysis of alpha-II-spectrin in the normal adult human brain |date=December 2001 | journal=Neurosci. Lett. | pages=41–4 | doi=10.1016/S0304-3940(01)02371-0| last1=Huh | first1=Gi-Yeong | last2=Glantz | first2=Susan B. | last3=Je | first3=Soojung | last4=Morrow | first4=Jon S. | last5=Kim | first5=Jung H. | s2cid=53270680 }}</ref> The hexagonal arrangements are formed by tetramers of spectrin subunits 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.  The protein is named spectrin since it was first isolated as a major protein component of human red blood cells which had been treated with mild detergents; the detergents [[Lysis|lysed]] the cells and the hemoglobin and other cytoplasmic components were washed out. In the light microscope the basic shape of the red blood cell could still be seen as the spectrin-containing submembranous cytoskeleton preserved the shape of the cell in outline. This became known as a red blood cell "ghost" (spectre), and so the major protein of the ghost was named spectrin. 

In certain types of brain injury such as [[diffuse axonal injury]], spectrin is irreversibly cleaved by the [[proteolysis|proteolytic]] [[enzyme]] [[calpain]], destroying the cytoskeleton.<ref name="Büki">{{cite journal | pmid = 10751434 | volume=20 | issue=8 | title=Cytochrome c release and caspase activation in traumatic axonal injury |date=April 2000 | journal=J. Neurosci. | pages=2825–34| last1 = Büki | first1 = A. | last2 = Okonkwo | first2 = D. O. | last3 = Wang | first3 = K. K. | last4 = Povlishock | first4 = J. T. | doi = 10.1523/JNEUROSCI.20-08-02825.2000 | doi-access = free | pmc = 6772193 }}</ref>  Spectrin cleavage causes the membrane to form [[Bleb (cell biology)|blebs]] and ultimately to be degraded, usually leading to the death of the cell.<ref name="Castillo and Babson">{{cite journal | last1 = Castillo | first1 = MR | last2 = Babson | first2 = JR. | year = 1998 | title = Ca<sup>2+</sup>-dependent mechanisms of cell injury in cultured cortical neurons | journal = Neuroscience | volume = 86 | issue = 4| pages = 1133–1144 | pmid = 9697120 | doi=10.1016/S0306-4522(98)00070-0| s2cid = 54228571 }}</ref> Spectrin subunits may also be cleaved by [[caspase]] family enzymes, and calpain and caspase produce different spectrin breakdown products which can be detected by [[western blotting]] with appropriate antibodies. Calpain cleavage may indicate activation of [[necrosis]], while caspase cleavage may indicate [[apoptosis]].<ref name="Li">{{cite journal | pmid = 21150538 | volume=69 | issue=6 | title=Biomarkers associated with diffuse traumatic axonal injury: exploring pathogenesis, early diagnosis, and prognosis. |date=December 2010 | journal=J. Trauma | pages=1610–1618 | doi=10.1097/TA.0b013e3181f5a9ed| last1=Li | first1=Jia | last2=Li | first2=Xue-Yuan | last3=Feng | first3=Dong-Fu | last4=Pan | first4=Dong-Chao }}</ref>

== 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. 

In humans, association with the intracellular face of the [[plasma membrane]] is by indirect interaction, through direct interactions with [[protein 4.1]] and [[ankyrin]], with the transmembrane ion transporter [[band 3]] Protein 4.2 binds the spectrin tail region to the transmembrane protein [[GYPA|glycophorin A]].<ref>Pathologic Basis of Disease, 8th edition  Robbins and Cotran (2010) page 642</ref> 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 rarely [[hereditary spherocytosis]].<ref>{{cite journal | last = Delaunay | first =J | title =Genetic disorders of the red cell membranes | journal =FEBS Letters | volume =369 | issue =1 | pages =34–37 | year =1995  | doi = 10.1016/0014-5793(95)00460-Q| pmid =7641880| doi-access =free }}</ref>

== In invertebrates ==
There are three spectrins in [[invertebrates]], α,β and β<sub>H</sub>. Mutations in  β<sub>H</sub> spectrin in ''[[Caenorhabditis elegans|C. elegans]]'' cause defects in morphogenesis resulting in a significantly shorter, but otherwise mostly normal, animal that moves and reproduces. These animals are called "sma" for their small phenotype and carry mutations in the ''[[Caenorhabditis elegans|C. elegans]]'' sma-1 gene. <ref name="McKeown">{{cite journal | last =McKeown  | first =C |author2=Praitis VM |author3=Austin JA  | title =sma-1 encodes a betaH-spectrin homolog required for Caenorhabditis elegans morphogenesis. | journal =Development| volume =125 | issue =11|pages = 2087–98 | year = 1998 | doi =10.1242/dev.125.11.2087 | url =http://dev.biologists.org/content/125/11/2087.long | pmid =9570773   | url-access =subscription }}</ref> A mutation in β spectrin in ''[[Caenorhabditis elegans|C. elegans]]'' results in an uncoordinated [[phenotype]] in which the worms are paralysed and much shorter than [[wild-type]].<ref name="Hammarlund">{{cite journal | last =Hammarlund  | first =M |author2=Davis WS |author3=Jorgensen EM  | title =Mutations in β-Spectrin Disrupt Axon Outgrowth and Sarcomere Structure | journal =Journal of Cell Biology| volume =149 | issue =4|pages = 931–942 | year = 2000 | doi = 10.1083/jcb.149.4.931| pmid =10811832  | pmc =2174563}}</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. melanogaster'' results in neurons that are morphologically normal but have reduced [[neurotransmission]] at the [[neuromuscular junction]].<ref name="Featherstone ">{{cite journal | last =Featherstone  | first =DE |author2=Davis WS |author3=Dubreuil RR |author4=Broadie K  | title =Drosophila alpha- and beta-spectrin mutations disrupt presynaptic neurotransmitter release | journal =Journal of Neuroscience | volume =21 | issue =12 | pages =4215–4224 | year =2001  | pmc=6762771 | doi = 10.1523/JNEUROSCI.21-12-04215.2001| pmid =11404407 | doi-access =free }}</ref>
In animals, spectrin forms the meshwork that provides red blood cells their shape.

== 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: [[SPTA1]], [[SPTAN1]]
* Beta: [[SPTB]], [[SPTBN1]], [[SPTBN2]], [[SPTBN4]], [[SPTBN5]]

The production of spectrin is promoted by the [[transcription factor]] [[GATA1]].

=== Role in muscle tissue ===
Some evidence for the role of spectrins in muscle tissues exist. In [[cardiac muscle|myocardial cell]]s, aII spectrin distribution is coincident with Z-discs and the plasma membrane of [[myofibrils]].<ref>{{cite journal | last =Bennett  | first =PM |author2=Baines AJ |author3=Lecomte MC |author4=Maggs AM |author5=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 | year =2004 | doi = 10.1023/B:JURE.0000035892.77399.51| pmid =15360127| s2cid =10297147 }}</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==
*{{Proteopedia|2fot}} the complex between [[calmodulin]] and alpha11spectrin
*[[Spectrin repeat]]
*[[Glycophorin C]], helps anchor spectrin-actin cytoskeleton to cell membrane in erythrocytes

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

{{Membrane proteins}}
{{Cytoskeletal Proteins}}

[[Category:Cytoskeleton]]