neuronal migration protein doublecortin; lissencephalin-X; Lis-X; doublin (DCX, DBCN, LISX)

Function

• microtubule-associated protein
• seems to be required for initial steps of neuronal dispersion & cortex lamination during cerebral cortex development
• may act by competing with the putative neuronal protein kinase DCAMKL1 in binding to a target protein
• may participate in a signaling pathway that is crucial for neuronal interaction before & during migration, possibly as part of a Ca+2-dependent signal transduction pathway
• may be part with LIS-1 of an overlapping, but distinct, signaling pathways that promote neuronal migration
• phosphorylation by MARK1, MARK2 & PKA regulates its ability to bind microtubules
• phosphorylation at Ser-346 & Ser-378 seems to occur only in neonatal brain; the levels falling precipitously by postnatal day 21
• interacts with tubulin
• interacts with USP9X

Structure

• contains 2 doublecortin domains

Compartment

• cytoplasm, cell projection

Alternative splicing

• named isoforms=5
• isoform LIS-XA possesses an alternative exon in 5' & is then translated from an upstream initiation codon
• isoform LIS-XB, isoform LIS-XC & isoform LIS-XD translation starts at the downstream initiation codon, resulting in absence of the 81 first amino acids
• isoform LIS-XC & isoform LIS-XD differ from isoform LIS-XB by a 5 amino acid & a 1 amino acid-insertion, respectively

Expression

• highly expressed in neuronal cells of fetal brain (in the majority of cells of the cortical plate, intermediate zone & ventricular zone), but not expressed in other fetal tissues
• in the adult, highly expressed in the brain frontal lobe, but very low expression in other regions of brain,
• not detected in heart, placenta, lung, liver, skeletal muscle, kidney & pancreas

Pathology

• defects in DCX are the cause of
  • lissencephaly X-linked type 1
  • subcortical band heterotopia X-linked
• chromosomal translocation t(X;2)(q22.3;p25.1) involving DCX is found in lissencephaly

Comparative biology

• expressed in dentate gyrus of female Sprague-Dawley rats
• doublecortin positive cells in the dentate gyrus decline 94-97% in old (26 months) vs young (4-6 month) old rats

More general terms

• microtubule-associated protein (MAP)
• phosphoprotein

Additional terms

• double cortex/X-linked lissencephaly syndrome; X-linked subcortical laminar heterotopia/lissencephaly syndrome; subcortical band heterotopia X-linked

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1641
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1641
• OMIM: https://mirror.omim.org/entry/300067
• OMIM: https://mirror.omim.org/entry/300121
• UniProt: http://www.uniprot.org/uniprot/O43602.html