# Spectrin

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Cytoskeletal protein

A schematic diagram of spectrin and other cytoskeletal molecules

Localization of alpha-II spectrin in green under the plasma membrane of rat neurons in tissue culture as shown with [confocal microscopy](/source/Confocal_microscopy) and [immunofluorescence](/source/Immunofluorescence). The nuclei of the cells is revealed in blue by the DNA dye [DAPI](/source/DAPI).

**Spectrin** is a [cytoskeletal](/source/Cytoskeleton) [protein](/source/Protein) that lines the intracellular side of the [plasma membrane](/source/Plasma_membrane) in many [eukaryotic cells](/source/Eukaryotic_cell), including [animal cells](/source/Animal_cell) but not in [plant cells](/source/Plant_cell) or [yeast](/source/Yeast).[1] Spectrin forms pentagonal or hexagonal arrangements, forming a [scaffold](/source/Scaffolding) and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure.[2] The hexagonal arrangements are formed by tetramers of spectrin subunits associating with short [actin](/source/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 [lysed](/source/Lysis) 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](/source/Diffuse_axonal_injury), spectrin is irreversibly cleaved by the [proteolytic](/source/Proteolysis) [enzyme](/source/Enzyme) [calpain](/source/Calpain), destroying the cytoskeleton.[3] Spectrin cleavage causes the membrane to form [blebs](/source/Bleb_(cell_biology)) and ultimately to be degraded, usually leading to the death of the cell.[4] Spectrin subunits may also be cleaved by [caspase](/source/Caspase) family enzymes, and calpain and caspase produce different spectrin breakdown products which can be detected by [western blotting](/source/Western_blotting) with appropriate antibodies. Calpain cleavage may indicate activation of [necrosis](/source/Necrosis), while caspase cleavage may indicate [apoptosis](/source/Apoptosis).[5]

## In erythrocytes

The convenience of using [erythrocytes](/source/Erythrocyte) 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](/source/Plasma_membrane) is by indirect interaction, through direct interactions with [protein 4.1](/source/Protein_4.1) and [ankyrin](/source/Ankyrin), with the transmembrane ion transporter [band 3](/source/Band_3) Protein 4.2 binds the spectrin tail region to the transmembrane protein [glycophorin A](/source/GYPA).[6] In animals, spectrin forms the meshwork that provides red blood cells their shape.

The [erythrocyte](/source/Erythrocyte) model demonstrates the importance of the spectrin cytoskeleton in that mutations in spectrin commonly cause hereditary defects of the erythrocyte, including [hereditary elliptocytosis](/source/Hereditary_elliptocytosis) and rarely [hereditary spherocytosis](/source/Hereditary_spherocytosis).[7]

## In invertebrates

There are three spectrins in [invertebrates](/source/Invertebrates), α, β and βH. Mutations in βH spectrin in *[Caenorhabditis elegans](/source/Caenorhabditis_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 *C. elegans* sma-1 gene.[8] A mutation in β spectrin in *C. elegans* results in an uncoordinated [phenotype](/source/Phenotype) in which the worms are paralysed and much shorter than [wild-type](/source/Wild-type).[9] In addition to the morphological effects, the Unc-70 mutation also produce defective [neurons](/source/Neurons). Neuron numbers are normal but neuronal outgrowth was defective.

Similarly, spectrin plays a role in *[Drosophila](/source/Drosophila)* neurons. Knock-out of α or β spectrin in *D. melanogaster* results in neurons that are morphologically normal but have reduced [neurotransmission](/source/Neurotransmission) at the [neuromuscular junction](/source/Neuromuscular_junction).[10] 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.[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*] 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.[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*]

In humans, the genes are:

- Alpha: [SPTA1](/source/SPTA1), [SPTAN1](/source/SPTAN1)

- Beta: [SPTB](/source/SPTB), [SPTBN1](/source/SPTBN1), [SPTBN2](/source/SPTBN2), [SPTBN4](/source/SPTBN4), [SPTBN5](/source/SPTBN5)

The production of spectrin is promoted by the [transcription factor](/source/Transcription_factor) [GATA1](/source/GATA1).[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*]

### Role in muscle tissue

Some evidence for the role of spectrins in muscle tissues exist. In [myocardial cells](/source/Cardiac_muscle), aII spectrin distribution is coincident with Z-discs and the plasma membrane of [myofibrils](/source/Myofibrils).[11] Additionally, mice with an ankyrin (ankB) knock-out have disrupted calcium homeostasis in the myocardial. Affected mice have disrupted z-band and sarcomere morphology. In this experimental model ryanodine and IP3 receptors have abnormal distribution in cultured myocytes. The [calcium signaling](/source/Calcium_signaling) of the cultured cells is disrupted. In humans, a mutation within the AnkB gene results in the [long QT syndrome](/source/Long_QT_syndrome) and sudden death, strengthening the evidence for a role for the spectrin cytoskeleton in excitable tissue.

## See also

- *[Proteopedia](/source/Proteopedia) [2fot](http://www.proteopedia.org/wiki/index.php/2fot)* the complex between [calmodulin](/source/Calmodulin) and alpha11spectrin

- [Spectrin repeat](/source/Spectrin_repeat)

- [Glycophorin C](/source/Glycophorin_C), helps anchor spectrin-actin cytoskeleton to cell membrane in erythrocytes

## References

1. **[^](#cite_ref-Li2022_1-0)** Li, D (8 August 2022). ["Role of Spectrin in Endocytosis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368487). *Cells*. **11** (15): 2459. [doi](/source/Doi_(identifier)):[10.3390/cells11152459](https://doi.org/10.3390%2Fcells11152459). [PMC](/source/PMC_(identifier)) [9368487](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368487). [PMID](/source/PMID_(identifier)) [35954302](https://pubmed.ncbi.nlm.nih.gov/35954302).

1. **[^](#cite_ref-Huh_2-0)** Huh, Gi-Yeong; Glantz, Susan B.; Je, Soojung; Morrow, Jon S.; Kim, Jung H. (December 2001). "Calpain proteolysis of alpha-II-spectrin in the normal adult human brain". *Neurosci. Lett*. **316** (1): 41–4. [doi](/source/Doi_(identifier)):[10.1016/S0304-3940(01)02371-0](https://doi.org/10.1016%2FS0304-3940%2801%2902371-0). [PMID](/source/PMID_(identifier)) [11720774](https://pubmed.ncbi.nlm.nih.gov/11720774). [S2CID](/source/S2CID_(identifier)) [53270680](https://api.semanticscholar.org/CorpusID:53270680).

1. **[^](#cite_ref-Büki_3-0)** Büki, A.; Okonkwo, D. O.; Wang, K. K.; Povlishock, J. T. (April 2000). ["Cytochrome c release and caspase activation in traumatic axonal injury"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772193). *J. Neurosci*. **20** (8): 2825–34. [doi](/source/Doi_(identifier)):[10.1523/JNEUROSCI.20-08-02825.2000](https://doi.org/10.1523%2FJNEUROSCI.20-08-02825.2000). [PMC](/source/PMC_(identifier)) [6772193](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772193). [PMID](/source/PMID_(identifier)) [10751434](https://pubmed.ncbi.nlm.nih.gov/10751434).

1. **[^](#cite_ref-Castillo_and_Babson_4-0)** Castillo, MR; Babson, JR. (1998). "Ca2+-dependent mechanisms of cell injury in cultured cortical neurons". *Neuroscience*. **86** (4): 1133–1144. [doi](/source/Doi_(identifier)):[10.1016/S0306-4522(98)00070-0](https://doi.org/10.1016%2FS0306-4522%2898%2900070-0). [PMID](/source/PMID_(identifier)) [9697120](https://pubmed.ncbi.nlm.nih.gov/9697120). [S2CID](/source/S2CID_(identifier)) [54228571](https://api.semanticscholar.org/CorpusID:54228571).

1. **[^](#cite_ref-Li_5-0)** Li, Jia; Li, Xue-Yuan; Feng, Dong-Fu; Pan, Dong-Chao (December 2010). "Biomarkers associated with diffuse traumatic axonal injury: exploring pathogenesis, early diagnosis, and prognosis". *J. Trauma*. **69** (6): 1610–1618. [doi](/source/Doi_(identifier)):[10.1097/TA.0b013e3181f5a9ed](https://doi.org/10.1097%2FTA.0b013e3181f5a9ed). [PMID](/source/PMID_(identifier)) [21150538](https://pubmed.ncbi.nlm.nih.gov/21150538).

1. **[^](#cite_ref-6)** Pathologic Basis of Disease, 8th edition Robbins and Cotran (2010) page 642

1. **[^](#cite_ref-7)** Delaunay, J (1995). ["Genetic disorders of the red cell membranes"](https://doi.org/10.1016%2F0014-5793%2895%2900460-Q). *FEBS Letters*. **369** (1): 34–37. [Bibcode](/source/Bibcode_(identifier)):[1995FEBSL.369...34D](https://ui.adsabs.harvard.edu/abs/1995FEBSL.369...34D). [doi](/source/Doi_(identifier)):[10.1016/0014-5793(95)00460-Q](https://doi.org/10.1016%2F0014-5793%2895%2900460-Q). [PMID](/source/PMID_(identifier)) [7641880](https://pubmed.ncbi.nlm.nih.gov/7641880).

1. **[^](#cite_ref-McKeown_8-0)** McKeown, C; Praitis VM; Austin JA (1998). ["sma-1 encodes a betaH-spectrin homolog required for Caenorhabditis elegans morphogenesis"](http://dev.biologists.org/content/125/11/2087.long). *Development*. **125** (11): 2087–98. [doi](/source/Doi_(identifier)):[10.1242/dev.125.11.2087](https://doi.org/10.1242%2Fdev.125.11.2087). [PMID](/source/PMID_(identifier)) [9570773](https://pubmed.ncbi.nlm.nih.gov/9570773).

1. **[^](#cite_ref-Hammarlund_9-0)** Hammarlund, M; Davis WS; Jorgensen EM (2000). ["Mutations in β-Spectrin Disrupt Axon Outgrowth and Sarcomere Structure"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174563). *Journal of Cell Biology*. **149** (4): 931–942. [doi](/source/Doi_(identifier)):[10.1083/jcb.149.4.931](https://doi.org/10.1083%2Fjcb.149.4.931). [PMC](/source/PMC_(identifier)) [2174563](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174563). [PMID](/source/PMID_(identifier)) [10811832](https://pubmed.ncbi.nlm.nih.gov/10811832).

1. **[^](#cite_ref-Featherstone_10-0)** Featherstone, DE; Davis WS; Dubreuil RR; Broadie K (2001). ["Drosophila alpha- and beta-spectrin mutations disrupt presynaptic neurotransmitter release"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762771). *Journal of Neuroscience*. **21** (12): 4215–4224. [doi](/source/Doi_(identifier)):[10.1523/JNEUROSCI.21-12-04215.2001](https://doi.org/10.1523%2FJNEUROSCI.21-12-04215.2001). [PMC](/source/PMC_(identifier)) [6762771](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762771). [PMID](/source/PMID_(identifier)) [11404407](https://pubmed.ncbi.nlm.nih.gov/11404407).

1. **[^](#cite_ref-11)** Bennett, PM; Baines AJ; Lecomte MC; Maggs AM; Pinder JC (2004). "Not just a plasma membrane protein: in cardiac muscle cells alpha-II spectrin also shows a close association with myofibrils". *Journal of Muscle Research and Cell Motility*. **25** (2): 119–126. [doi](/source/Doi_(identifier)):[10.1023/B:JURE.0000035892.77399.51](https://doi.org/10.1023%2FB%3AJURE.0000035892.77399.51). [PMID](/source/PMID_(identifier)) [15360127](https://pubmed.ncbi.nlm.nih.gov/15360127). [S2CID](/source/S2CID_(identifier)) [10297147](https://api.semanticscholar.org/CorpusID:10297147).

v t e Protein: cell membrane proteins (other than Cell surface receptor, enzymes, and cytoskeleton) Arrestin SAG ARRB1 ARRB2 ARR3 Membrane-spanning 4A MS4A1 MS4A2 MS4A3 MS4A4A MS4A4E MS4A5 MS4A6A MS4A6E MS4A7 MS4A8B MS4A9 MS4A10 MS4A12 MS4A13 MS4A14 MS4A15 MS4A18 Myelin Myelin basic protein PMP2 Myelin proteolipid protein PLP1 Myelin oligodendrocyte glycoprotein Myelin-associated glycoprotein Myelin protein zero Pulmonary surfactant Pulmonary surfactant-associated protein B Pulmonary surfactant-associated protein C Tetraspanin TSPAN1 TSPAN2 TSPAN3 TSPAN4 TSPAN5 TSPAN6 TSPAN7 TSPAN8 TSPAN9 TSPAN10 TSPAN11 TSPAN12 TSPAN13 TSPAN14 TSPAN15 TSPAN16 TSPAN17 TSPAN18 TSPAN19 TSPAN20 TSPAN21 TSPAN22 TSPAN23 TSPAN24 TSPAN25 TSPAN26 TSPAN27 TSPAN28 TSPAN29 TSPAN30 TSPAN31 TSPAN32 TSPAN33 TSPAN34 Other/ungrouped Calnexin LDL-receptor-related protein-associated protein Neurofibromin 2 Presenilin PSEN1 PSEN2 HFE Phospholipid transfer proteins Dysferlin STRC OTOF see also other cell membrane protein disorders

v t e Proteins of the cytoskeleton Human Microfilaments and ABPs Myofilament Actins A1 A2 B C1 G1 G2 Myosins I MYO1A MYO1B MYO1C MYO1D MYO1E MYO1F MYO1G MYO1H II MYH1 MYH2 MYH3 MYH4 MYH6 MYH7 MYH7B MYH8 MYH9 MYH10 MYH11 MYH13 MYH14 MYH15 MYH16 III MYO3A MYO3B V MYO5A MYO5B MYO5C VI MYO6 VII MYO7A MYO7B IX MYO9A MYO9B X MYO10 XV MYO15A XVIII MYO18A MYO18B LC MYL1 MYL2 MYL3 MYL4 MYL5 MYL6 MYL6B MYL7 MYL9 MYLIP MYLK MYLK2 MYLL1 Other Tropomodulin 1 2 3 4 Troponin T 1 2 3 C 1 2 I 1 2 3 Tropomyosin 1 2 3 4 Actinin 1 2 3 4 Arp2/3 complex actin depolymerizing factors Cofilin 1 2 Destrin Gelsolin Profilin 1 2 Titin Other Wiskott–Aldrich syndrome protein Fibrillin Filamin FLNA FLNB FLNC Espin TRIOBP Intermediate filaments Type 1/2 (Keratin, Cytokeratin) Epithelial keratins (soft alpha-keratins) type I/chromosome 17 9 10 12 13 14 15 16 17 19 20 chromosome 12 18 none 21 type II/chromosome 12 1 2A 3 4 5 6A 6B 6C 7 8 Hair keratins (hard alpha-keratins) type I/chromosome 17 31 32 33A 33B 34 35 36 37 38 type II/chromosome 12 81 82 83 84 85 86 Ungrouped alpha chromosome 17 23 24 25 26 27 28 39 40 chromosome 12 71 72 73 74 75 76 77 78 79 80 Not alpha Beta-keratin Type 3 Desmin GFAP Peripherin Vimentin Type 4 Internexin Nestin Neurofilament NEFL NEFM NEFH Synemin Syncoilin Type 5 Nuclear lamins A/C B1 B2 Microtubules and MAPs Tubulins TUBA1A TUBA1B TUBA1C TUBA3C TUBA3D TUBA3E TUBA4A TUBA8 TUBB TUBB1 TUBB2A TUBB2B TUBB2C TUBB3 TUBB4A TUBB4Q TUBB6 TUBB8 TUBG1 TUBG2 TUBGCP2 TUBGCP3 TUBGCP4 TUBGCP5 TUBGCP6 TUBD1 TUBE1 MAPs EB1 EB2 EB3 MAP1A MAP1B MAP2 MAP4 Kinesins KIF1A KIF1B KIF2A KIF2C KIF3B KIF3C KIF4A KIF4B KIF5A KIF5B KIF5C KIF6 KIF7 KIF9 KIF11 KIF12 KIF13A KIF13B KIF14 KIF15 KIF16B KIF17 KIF18A KIF18B KIF19 KIF20A KIF20B KIF21A KIF21B KIF22 KIF23 KIF24 KIF25 KIF26A KIF26B KIF27 KIFC1 KIFC2 KIFC3 Dyneins axonemal: DNAH1 DNAH2 DNAH3 DNAH5 DNAH6 DNAH7 DNAH8 DNAH9 DNAH10 DNAH11 DNAH12 DNAH13 DNAH14 DNAH17 DNAI1 DNAI2 DNALI1 DNAL1 DNAL4 cytoplasmic: DYNC1H1 DYNC2H1 DYNC1I1 DYNC1I2 DYNC1LI1 DYNC1LI2 DYNC2LI1 DYNLL1 DYNLL2 DYNLRB1 DYNLRB2 DYNLT1 DYNLT3 Microtubule organising proteins CAMSAP1 CAMSAP2 CAMSAP3 Centrin 1 Centrin 2 Centrin 3 PCM1 Microtubule severing proteins Katanin Spastin Other Tau protein Dynactin DCTN1 Stathmin Tektin TEKT1 TEKT2 TEKT3 TEKT4 TEKT5 Dynamin DNM1 DNM2 DNM3 Catenins Alpha catenin Beta catenin APC Plakoglobin (gamma catenin) Delta catenin GAN Membrane Dystrophin Dystroglycan Utrophin Ankyrin ANK1 ANK2 ANK3 Spectrin SPTA1 SPTAN1 SPTB SPTBN1 SPTBN2 SPTBN4 SPTBN5 Other Plakins Corneodesmosin Desmoplakin Dystonin Envoplakin MACF1 Periplakin Plectin Talin TLN1 Vinculin Plakophilin PKP1 PKP2 ACF7 PLEKHA7 Nonhuman Major sperm proteins Prokaryotic cytoskeleton Crescentin FtsZ MreB ParM See also: cytoskeletal defects

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Adapted from the Wikipedia article [Spectrin](https://en.wikipedia.org/wiki/Spectrin) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Spectrin?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.