Spectrin

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Spectrin is a 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 (Huh et al., 2001). 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 (Liu et al., 1987).

In certain types of brain injury such as diffuse axonal injury, spectrin is irreversibly cleaved by the proteolytic enzyme calpain, destroying the cytosketelon (Büki et al., 2000). Spectrin cleavage causes the membrane to form blebs and ultimately to be degraded, usually leading to the death of the cell (Castillo and Babson, 1998).

Contents 1 Spectrin in erythrocytes 2 Spectrin in invertebrates 3 Spectrin in vertebrates 3.1 Vertebrate spectrin genes 3.2 Role of spectrin in muscle tissue 4 References

[edit] Spectrin in erythrocytes

The simplicity and ease of acquisition of the erythrocyte means that it has become the standard model for the investigation of the spectrin cytoskeleton (Lux, 1979). Tetrameric spectrin is formed by the lateral association of αI and ßI 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.

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 (Delaunay, 1995).

[edit] Spectrin in invertebrates

There are three spectrins in invertebrates, α,β and β_H. A mutation in β spectrin in C. elegans results in an unco-ordinated phenotype in which the worms are paralysed and much shorter than wild-type (Hammarlund et al, 2000). 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 (Featherstone et al, 2001).

[edit] Spectrin in vertebrates

[edit] 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

[edit] Role of spectrin in muscle tissue

Some evidence for the role of spectrins in muscle tissues exist. In myocardia αII spectrin distribution is co-incident with Z-discs and the plasma membrane of myofibrils (Bennett et al, 2004). 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 IP₃ receptors have abnormal distribution in cultured myocytes. The calcium signaling of the cultured cells is disrupted (Tuvia et al, 1999). 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 (as reviewed by Baines and Pinder, 2005).

[edit] References

• Büki A, Okonkwo D. O., Wang K. K. W., and Povlishock J. T. (2000). Cytochrome c Release and Caspase Activation in Traumatic Axonal Injury. Journal of Neuroscience. 20(8): 2825-2834. <http://www.jneurosci.org/cgi/content/abstract/20/8/2825>
• Castillo M. R. and Babson J. R. (1998). Ca2+-dependent mechanisms of cell injury in cultured cortical neurons. Neuroscience. 86(4): 1133-1144. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9697120&dopt=Abstract>
• Huh G. Y., Glantz S. B., Je S, Morrow J. S., and Kim J. H. (2001). Calpain proteolysis of alphaII-spectrin in the normal adult human brain. Neuroscience Letters. 316(1): 41-44. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11720774&dopt=Citation>
• Karp G. 2005. Cell and Molecular Biology: Concepts and Experiments, Fourth ed, pp. 148, 165-170, and 624-664. John Wiley and Sons, Hoboken, NJ.
• Liu SC, Derick LH, Palek J. Visualization of the hexagonal lattice in the erythrocyte membrane skeleton. J Cell Biol. 1987 Mar;104(3):527-36.
• Lux SE. Dissecting the red cell membrane skeleton. Nature. 1979 Oct 11;281(5731):426-9.
• Delaunay J. Genetic disorders of the red cell membranes. FEBS Lett. 1995 Aug 1;369(1):34-7.
• Hammarlund M, Davis WS, Jorgensen EM. Mutations in beta-spectrin disrupt axon outgrowth and sarcomere structure. J Cell Biol. 2000 May 15;149(4):931-42.
• Featherstone DE, Davis WS, Dubreuil RR, Broadie K. Drosophila alpha- and beta-spectrin mutations disrupt presynaptic neurotransmitter release. J Neurosci. 2001 Jun 15;21(12):4215-24.
• Bennett PM, Baines AJ, Lecomte MC, Maggs AM, Pinder JC. Not just a plasma membrane protein: in cardiac muscle cells alpha-II spectrin also shows a close association with myofibrils. J Muscle Res Cell Motil. 2004;25(2):119-26.
• Tuvia S, Buhusi M, Davis L, Reedy M, Bennett V. Ankyrin-B is required for intracellular sorting of structurally diverse Ca2+ homeostasis proteins. J Cell Biol. 1999 Nov 29;147(5):995-1008.
• Baines AJ, Pinder JC. The spectrin-associated cytoskeleton in mammalian heart. Front Biosci. 2005 Sep 1;10:3020-33.