| DCX | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | DCX , DBCN, DC, LISX, SCLH, XLIS, doublecortin | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 300121 MGI: 1277171 HomoloGene: 7683 GeneCards: DCX | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
Neuronal migration protein doublecortin, also known as doublin or lissencephalin-X is a protein that in humans is encoded by the DCX gene. [5]
Doublecortin (DCX) is a microtubule-associated protein expressed by neuronal precursor cells and immature neurons in embryonic and adult cortical structures. Neuronal precursor cells begin to express DCX while actively dividing, and their neuronal daughter cells continue to express DCX for 2–3 weeks as the cells mature into neurons. Downregulation of DCX begins after 2 weeks, and occurs at the same time that these cells begin to express NeuN, a neuronal marker. [7]
Due to the nearly exclusive expression of DCX in developing neurons, this protein has been used increasingly as a marker for neurogenesis. Indeed, levels of DCX expression increase in response to exercise, [8] and that increase occurs in parallel with increased BrdU labeling, which is currently a "gold standard" in measuring neurogenesis.
Doublecortin was found to bind to the microtubule cytoskeleton. In vivo and in vitro assays show that Doublecortin stabilizes microtubules and causes bundling. [9] Doublecortin is a basic protein with an iso-electric point of 10 typical of microtubule-binding proteins.
In mice where the Doublecortin gene has been knocked out, cortical layers are still correctly formed. However, the hippocampi of these mice show disorganisation in the CA3 region. The normally single layer of pyramidal cells in mutants is seen as a double layer. These mice also have different behavior than their wild type littermates and are epileptic. [10]
| Doublecortin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 solution structure of the N-terminal dcx domain of human doublecortin-like kinase | |||||||||
| Identifiers | |||||||||
| Symbol | DCX | ||||||||
| Pfam | PF03607 | ||||||||
| InterPro | IPR003533 | ||||||||
| SCOP2 | 1mfw / SCOPe / SUPFAM | ||||||||
| CDD | cd01617 | ||||||||
| |||||||||
The detailed sequence analysis of Doublecortin and Doublecortin-like proteins allowed the identification of a tandem repeat of evolutionarily conserved Doublecortin (DC) domains. These domains are found in the N terminus of proteins and consists of tandemly repeated copies of an around 80 amino acids region. It has been suggested that the first DC domain of Doublecortin binds tubulin and enhances microtubule polymerisation. [11]
Doublecortin has been shown to influence the structure of microtubules. Microtubule nucleated in vitro in the presence of Doublecortin have almost exclusively 13 protofilaments, whereas microtubule nucleated without Doublecortin are present in a range of different sizes.
Doublecortin is mutated in X-linked lissencephaly and the double cortex syndrome, and the clinical manifestations are sex-linked. In males, X-linked lissencephaly produces a smooth brain due to lack of migration of immature neurons, which normally promote folding of the brain surface. Double cortex syndrome is characterized by abnormal migration of neural tissue during development which results in two bands of misplaced neurons within the subcortical white, generating two cortices, giving the name to the syndrome; this finding generally occurs in females. [13] The mutation was discovered by Joseph Gleeson and Christopher A. Walsh in Boston. [14] [15] At least 49 disease-causing mutations in this gene have been discovered. [16]
Lissencephaly is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in a lack of development of brain folds (gyri) and grooves (sulci). It is a form of cephalic disorder. Terms such as agyria and pachygyria are used to describe the appearance of the surface of the brain.
Pachygyria is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. Typically, children have developmental delay and seizures, the onset and severity depending on the severity of the cortical malformation. Infantile spasms are common in affected children, as is intractable epilepsy.
Treacle protein is a protein that in humans is encoded by the TCOF1 gene.
Gray matter heterotopia is a neurological disorder caused by gray matter being located in an atypical location in the brain.
Platelet-activating factor acetylhydrolase IB subunit alpha is an enzyme that in humans is encoded by the PAFAH1B1 gene. The protein is often referred to as Lis1 and plays an important role in regulating the motor protein Dynein.
Wolframin is a protein that in humans is encoded by the WFS1 gene.
Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.
Eyes absent homolog 1 is a protein that in humans is encoded by the EYA1 gene.
Filamin B, beta (FLNB), also known as Filamin B, beta , is a cytoplasmic protein which in humans is encoded by the FLNB gene.
Gap junction beta-3 protein (GJB3), also known as connexin 31 (Cx31) — is a protein that in humans is encoded by the GJB3 gene.
Nuclear distribution protein nudE homolog 1 is a protein that in humans is encoded by the NDE1 gene.
Oral-facial-digital syndrome 1 protein is a protein that in humans is encoded by the OFD1 gene.
Ceroid-lipofuscinosis neuronal protein 5 is a protein that in humans is encoded by the CLN5 gene.
Katanin p80 WD40-containing subunit B1 is a protein that in humans is encoded by the KATNB1 gene.
Tripartite motif-containing protein 32 is a protein that in humans is encoded by the TRIM32 gene. Since its discovery in 1995, TRIM32 has been shown to be implicated in a number of diverse biological pathways.
Serine/threonine-protein kinase DCLK1 is an enzyme that in humans is encoded by the DCLK1 gene.
Dentatorubral–pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar degeneration caused by an expansion of a CAG repeat encoding a polyglutamine tract in the atrophin-1 protein. It is also known as Haw River Syndrome and Naito–Oyanagi disease. Although this condition was perhaps first described by Smith et al. in 1958, and several sporadic cases have been reported from Western countries, this disorder seems to be very rare except in Japan.
The development of the cerebral cortex, known as corticogenesis is the process during which the cerebral cortex of the brain is formed as part of the development of the nervous system of mammals including its development in humans. The cortex is the outer layer of the brain and is composed of up to six layers. Neurons formed in the ventricular zone migrate to their final locations in one of the six layers of the cortex. The process occurs from embryonic day 10 to 17 in mice and between gestational weeks seven to 18 in humans.
Cajal–Retzius cells are a heterogeneous population of morphologically and molecularly distinct reelin-producing cell types in the marginal zone/layer I of the developmental cerebral cortex and in the immature hippocampus of different species and at different times during embryogenesis and postnatal life.
Neurotubules are microtubules found in neurons in nervous tissues. Along with neurofilaments and microfilaments, they form the cytoskeleton of neurons. Neurotubules are undivided hollow cylinders that are made up of tubulin protein polymers and arrays parallel to the plasma membrane in neurons. Neurotubules have an outer diameter of about 23 nm and an inner diameter, also known as the central core, of about 12 nm. The wall of the neurotubules is about 5 nm in width. There is a non-opaque clear zone surrounding the neurotubule and it is about 40 nm in diameter. Like microtubules, neurotubules are greatly dynamic and the length of them can be adjusted by polymerization and depolymerization of tubulin.
Media related to Doublecortin at Wikimedia CommonsPDB gallery | |
|---|---|
|
