Spectrin
Encyclopedia
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. 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 proteolytic
enzyme
calpain
, destroying the cytosketelon. Spectrin cleavage causes the membrane to form blebs
and ultimately to be degraded, usually leading to the death of the cell.
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
.
results in an uncoordinated phenotype
in which the worms are paralysed and much shorter than wild-type. 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
.
In animals, spectrin forms the meshwork that provides red blood cells their shape.
In humans, the genes are:
The production of spectrin is promoted by the transcription factor
GATA1
.
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.
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding
Scaffolding
Scaffolding is a temporary structure used to support people and material in the construction or repair of buildings and other large structures. It is usually a modular system of metal pipes or tubes, although it can be from other materials...
and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure. The hexagonal arrangements are formed by tetramers of spectrin associating with short actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
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
Diffuse axonal injury
Diffuse axonal injury is one of the most common and devastating types of traumatic brain injury, meaning that damage occurs over a more widespread area than in focal brain injury. DAI, which refers to extensive lesions in white matter tracts, is one of the major causes of unconsciousness and...
, spectrin is irreversibly cleaved by the proteolytic
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
calpain
Calpain
A calpain is a protein belonging to the family of calcium-dependent, non-lysosomal cysteine proteases expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan CA in the MEROPS database...
, destroying the cytosketelon. Spectrin cleavage causes the membrane to form blebs
Bleb (cell biology)
In cell biology, a bleb is an irregular bulge in the plasma membrane of a cell caused by localized decoupling of the cytoskeleton from the plasma membrane...
and ultimately to be degraded, usually leading to the death of the cell.
Spectrin in erythrocytes
The convenience of using erythrocytes 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
Ankyrin
Ankyrins are a family of adaptor proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane skeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins...
, 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
Hereditary elliptocytosis
Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the sufferer's erythrocytes are elliptical rather than the typical biconcave disc shape. It is one of many red-cell membrane defects. In its severe forms, this disorder...
and hereditary spherocytosis
Hereditary spherocytosis
Hereditary spherocytosis is a genetically-transmitted form of spherocytosis, an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped , and therefore more prone to hemolysis.-Symptoms:As in non-hereditary spherocytosis,...
.
Spectrin in invertebrates
There are three spectrins in invertebrates, α,β and βH. A mutation in β spectrin in C. elegansCaenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
results in an uncoordinated phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
in which the worms are paralysed and much shorter than wild-type. 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
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
neurons. Knock-out of α or β spectrin in D. melanogaster results in neurons that are morphologically normal but have reduced neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
at the neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
.
In animals, spectrin forms the meshwork that provides red blood cells their shape.
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: SPTA1SPTA1Spectrin alpha chain, erythrocyte is a protein that in humans is encoded by the SPTA1 gene.-Interactions:Spectrin, alpha 1 has been shown to interact with Abl gene.-Further reading:...
, SPTAN1SPTAN1Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene.The spectrins are a family of widely-distributed cytoskeletal proteins which are involved in actin crosslinking. The protein enocoded by this gene is a spectrin alpha-chain which heterodimerizes with... - Beta: SPTBSPTBSpectrin beta chain, erythrocyte is a protein that in humans is encoded by the SPTB gene.-Further reading:...
, SPTBN1SPTBN1Spectrin beta chain, brain 1 is a protein that in humans is encoded by the SPTBN1 gene.-Interactions:SPTBN1 has been shown to interact with Merlin.-Further reading:...
, SPTBN2SPTBN2Spectrin beta chain, brain 2 is a protein that in humans is encoded by the SPTBN2 gene.-Interactions:SPTBN2 has been shown to interact with UNC13B, ACTR1A and Beta-actin.-Further reading:...
, SPTBN4SPTBN4Spectrin, beta, non-erythrocytic 4, also known as SPTBN4, is a protein which in humans is encoded by the SPTBN4 gene.Spectrin is an actin crosslinking and molecular scaffold protein that links the cell membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement...
, SPTBN5SPTBN5Spectrin, beta, non-erythrocytic 5 also known as SPTBN5 is a protein which in humans is encoded by the SPTBN5 gene. SPTBN5 belongs to the spectrin family of cytoskeletal proteins.- Structure and function :SPTBN5 contains the following domains:...
The production of spectrin is promoted by the transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
GATA1
GATA1
Erythroid transcription factor also known as GATA-binding factor 1 or GATA-1 is a protein that in humans is encoded by the GATA1 gene....
.
Role of spectrin in muscle tissue
Some evidence for the role of spectrins in muscle tissues exist. In myocardial cells, αII spectrin distribution is coincident with Z-discs and the plasma membrane of myofibrils. 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 signalingCalcium signaling
Calcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins...
of the cultured cells is disrupted.
In humans, a mutation within the AnkB gene results in the long QT syndrome
Long QT syndrome
The long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation...
and sudden death, strengthening the evidence for a role for the spectrin cytoskeleton in excitable tissue.