Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca2+-dependent signaling protein which is mutated in human X-linked neuronal migration defects
Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca2+-dependent signaling protein which is mutated in human X-linked neuronal migration defects
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DOI：
10.1093/hmg/7.8.1327
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发表时间：
1998-08-01
影响因子：
3.5
通讯作者：
Srivastava, AK
中科院分区：
文献类型：
--
作者：
Sossey-Alaoui, K;Hartung, AJ;Srivastava, AK
皮质下带状异位（SBH）和经典无脑畸形（LIS）是由于神经元迁移不足引起的智力低下和癫痫。通过连锁分析和X12易位断裂点的物理作图，定位了Xq22.3-q24上的一个LIS/SBH基因座。最近鉴定的一个基因，doublecortin（DCX），在胎儿脑中表达并在LIS/SBH患者中突变。我们已经确定了四个新的错义突变的基因，一个家族性突变与LIS的男性和SBH的携带者女性，一个从头突变的SBH女性，和两个突变的散发性SBH女性患者。DCX基因仅在成年人额叶高水平表达，我们还克隆了X连锁小鼠双皮质素（Dcx）基因。它编码高度亲水性40 kDa蛋白质的同种型，与其人类对应物同源，并含有几个潜在的磷酸化位点。人和小鼠DCX蛋白都与含有Ca 2 +/钙调蛋白激酶结构域的CNS蛋白同源，这表明DCX蛋白可能属于一类通过Ca 2+依赖性信号传导参与神经元迁移的新型细胞内蛋白。
Subcortical band heterotopia (SBH) and classical lissencephaly (LIS) result from deficient neuronal migration which causes mental retardation and epilepsy. A single LIS/SBH locus on Xq22.3-q24 was mapped by linkage analysis and physical mapping of the breakpoint in an X;2 translocation, A recently identified gene, doublecortin (DCX), is expressed in fetal brain and mutated in LIS/SBH patients. We have identified four novel missense mutations in the gene, one familial mutation with LIS in a male and SBH in the carrier females, one de novo mutation in an SBH female, and two mutations in sporadic SBH female patients. The DCX gene is found to be expressed exclusively at a very high level in the adult frontal lobe, We have also cloned the X-linked mouse doublecortin (Dcx) gene. It encodes isoforms of a highly hydrophilic 40 kDa protein, homologous to its human counterpart and containing several potential phosphorylation sites. Both human and mouse DCX proteins are homologous to a CNS protein containing a Ca2+/calmodulin kinase domain, suggesting that the DCX protein may belong to a novel class of intracellular proteins involved in neuronal migration through Ca2+-dependent signaling.