Doublecortin

DCX
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ATU, 1MJD, 2BQQ, 2XRP, 5IN7, 5IOI, 5IKC, 5IP4, 5IO9
Identifiers
Aliases	DCX, DBCN, DC, LISX, SCLH, XLIS, doublecortin
External IDs	OMIM: 300121; MGI: 1277171; HomoloGene: 7683; GeneCards: DCX; OMA:DCX - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xq23 Start 111,293,779 bp[1] End 111,412,429 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X F2 Start 142,638,838 bp[2] End 142,716,307 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence ventricular zone tail of epididymis endothelial cell Brodmann area 23 middle temporal gyrus secondary oocyte primary visual cortex Brodmann area 10 Brodmann area 46 Top expressed in Rostral migratory stream trigeminal ganglion barrel cortex ganglionic eminence medial ganglionic eminence superior cervical ganglion human fetus fossa neural tube olfactory bulb More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding protein kinase binding microtubule binding Cellular component cell projection microtubule associated complex microtubule cytoskeleton cytosol neuron projection cytoplasm axoneme Biological process cell differentiation nervous system development multicellular organism development central nervous system development neuron migration intracellular signal transduction axoneme assembly photoreceptor cell development retina development in camera-type eye Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1641 13193 Ensembl ENSG00000077279 ENSMUSG00000031285 UniProt O43602 O88809 RefSeq (mRNA) NM_000555 NM_001195553 NM_178151 NM_178152 NM_178153 NM_001369370 NM_001369371 NM_001369372 NM_001369373 NM_001369374 NM_001110222 NM_001110223 NM_001110224 NM_010025 RefSeq (protein) NP_000546 NP_001182482 NP_835364 NP_835365 NP_835366 NP_001356299 NP_001356300 NP_001356301 NP_001356302 NP_001356303 NP_001103692 NP_001103693 NP_001103694 NP_034155 Location (UCSC) Chr X: 111.29 – 111.41 Mb Chr X: 142.64 – 142.72 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Neuronal migration protein doublecortin, also known as doublin or lissencephalin-X is a protein that in humans is encoded by the DCX gene.^[5]

Function

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.

Knock out mouse

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]

Structure

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
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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.

Interactions

Doublecortin has been shown to interact with PAFAH1B1.^[12]

Clinical significance

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]

See also

• Lissencephaly

References

Further reading

External links

• Media related to Doublecortin at Wikimedia Commons
• GeneReviews/NCBI/NIH/UW entry on DCX-Related Disorders
• OMIM entries on DCX-Related Disorders
• doublecortin+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: O43602 (Neuronal migration protein doublecortin) at the PDBe-KB.