Disease relevance of DCX

• Here we propose the use of the doublecortin (DCX) gene as a new molecular marker of neuroblastoma cells [1].
• DCX was highly phosphorylated in glioma cells [2].
• In univariate analysis, high midazolam concentration and free DCX AUC were associated with severe neutropenia and FN [3].
• By multivariate analysis, total DCX AUC and baseline lymphopenia were associated with FN [3].
• Using two paradigms increasing neurogenesis levels (physical activity and epileptic seizures), we demonstrate that quantification of DCX-expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis [4].

Psychiatry related information on DCX

• DCX mutations cause mental retardation in male subjects with lissencephalypachygyria and in female subjects with subcortical band heterotopia (SBH) [5].
• Periods rich in slow-wave sleep (SWS) not only facilitate the consolidation of declarative memories, but in humans, SWS is also accompanied by a pronounced endogenous transcortical DC potential shift of negative polarity over frontocortical areas [6].

High impact information on DCX

• The protein encoded by this gene is 2,156 amino acids and its function is currently unknown, although the amino terminus has similarity to that of the doublecortin protein, whose gene (DCX) has been implicated in lissencephaly in humans [7].
• A novel lysosome-associated membrane glycoprotein, DC-LAMP, induced upon DC maturation, is transiently expressed in MHC class II compartment [8].
• This suggests that DC-LAMP might change the lysosome function after the transfer of peptide-MHC class II molecules to the surface of DC [8].
• Functionally, preincubation of DCs or resting T cells with blocking neuropilin-1 antibodies inhibited DC-induced proliferation of resting T cells [9].
• Several studies using in utero electroporation and RNAi have revealed that transition out of the multipolar stage depends on the function of filamin A, LIS1 and DCX [10].

Chemical compound and disease context of DCX

• The present study examined DC shifts induced by hyperventilation in healthy human subjects under the influence of the benzodiazepine, clonazepam, which is used as anticonvulsant [11].
• Acute myeloid leukemia has been observed in FA, DBA, DC, SD, SCN, and Amega, although not yet in TAR patients [12].
• We have previously reported that a novel enzyme, L-2,4-diaminobutyrate decarboxylase (DABA DC), which is responsible for the formation of 1,3-diaminopropane, occurs in two Acinetobacter species [13].

Biological context of DCX

• In the large majority of patients, missense mutations in DCX fall within the conserved regions [14].
• Mutations in the X-linked gene doublecortin ( DCX ) result in lissencephaly in males or subcortical laminar heterotopia ('double cortex') in females [14].
• Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia [15].
• Point mutations in XLIS identified the C-terminal serine/proline-rich region as potentially important for protein function [16].
• The X-linked subcortical laminar heterotopia and lissencephaly syndrome is a disorder of neuronal migration caused by a mutation in XLIS, a recently cloned gene on chromosome Xq22.3-q23 [17].

Anatomical context of DCX

• In functional assays, the N-terminal DCX domain of doublecortin binds only to assembled microtubules, whereas the C-terminal domain binds to both microtubules and unpolymerized tubulin [18].
• To study the functional consequences of DCX mutations, we overexpressed seven of the reported mutations in COS7 cells and examined their effect on the microtubule cytoskeleton [14].
• The neuronal migration protein doublecortin (DCX) that associates with microtubules through a tandem DCX repeat, is required for the development of the complex architecture of the human cerebral cortex [19].
• DCX immunoreactivity was apparently reduced in ZS, particularly in the cortical plate of fetuses, and in the subependymal foci of heterotopic neurons of the infants [20].
• Both LIS1 and DCX participate in the development of GABAergic interneurons as well as pyramidal neurons, while ARX participates only in that of interneurons [21].

Associations of DCX with chemical compounds

• DCX immunocytochemistry showed that immature hippocampal cells of rats exposed to cocaine displayed normal arborization patterns and similar degrees of colocalization with BrdU at two different developmental stages [22].
• The rate of adult neurogenesis is doubled in the dentate gyrus of Bcl-2-overexpressing mice as demonstrated by quantification of progenitor cells using DCX and new neurons using bromodeoxyuridine (BrdU)/neuronal nuclei antigen (NeuN) double-labelling [23].
• Following induction of lesions by striatal injection of 6-OHDA or QA, the number of cells positive for doublecortin (DCX) was strongly increased in the striatum; however, there was no change in the number of DCX-positive cells following 6-OHDA injection into the SN [24].
• The data also suggest that the synapses on DCX-labeled hilar basal dendrites contribute to the persistence of hilar basal dendrites on neurons born after pilocarpine-induced seizures [25].
• DCX was purified by preparative thin layer chromatography from chloroform: methanol = 4:1 extracts of whole bacteria, and is chromatographically homogeneous [26].

Physical interactions of DCX

• Furthermore, endogenous DCX could be co-immunoprecipitated with endogenous LIS1 in embryonic brain extracts, demonstrating an in vivo association [27].

Regulatory relationships of DCX

• Epitope-tagged DCX transiently expressed in COS cells can be co-immunoprecipitated with endogenous LIS1 [27].
• During brain development DCLK is expressed mainly in postmigratory neurons in a similar pattern to DCX [28].

Other interactions of DCX

• The distinct LIS patterns suggest that LIS1 and XLIS may be part of overlapping, but distinct, signaling pathways that promote neuronal migration [16].
• We expressed DCX or DCLK (KIAA0369) repeats in vitro and in vivo [14].
• A YAC contig in Xq22.3-q23, from DXS287 to DXS8088, spanning the brain-specific genes doublecortin (DCX) and PAK3 [29].
• Missense DCX mutations may manifest as non-syndromic mental retardation with cryptogenic epilepsy in female subjects and SBH in boys [5].
• The extensive co-localization of DCX and Calretinin in non-radially oriented neurons suggested a non-pyramidal phenotype [30].

Analytical, diagnostic and therapeutic context of DCX

• Here, we performed a detailed sequence analysis of DCX and DCX-like proteins from various organisms and defined an evolutionarily conserved Doublecortin (DC) domain [14].
• Reduced expression of DCX in ZS was confirmed by Western blot analysis [20].
• In type I or classical lissencephaly, two genetic causes, namely the LIS1 gene mapping at 17p13.3 and the DCX (doublecortin on X) gene mapping at Xq22.3 are involved [31].
• Mutations of LIS1 were found by sequencing ( n = 8) and Southern blot ( n = 2) in a total of 10 patients (40%) of both sexes and mutations of XLIS in five males (20%) [16].
• Polymerase chain reaction (PCR) disclosed a deletion of part of the DCX gene in one male ILS patient [32].

References