Mutations in the doublecortin (DCX) gene, which encodes a microtubule-binding protein, cause human cortical malformations, including lissencephaly and subcortical band heterotopia. A deficiency in DCX and doublecortin-like kinase 1 (DCLK1), a functionally redundant and structurally similar cognate of DCX, decreases neurite length and increases the number of primary neurites directly arising from the soma. The underlying mechanism is not completely understood. In this study, the elongation of the somatic Golgi apparatus into proximal dendrites, which have been implicated in dendrite patterning, was significantly decreased in the absence of DCX/DCLK1. Phosphorylation of DCX at S47 or S327 was involved in this process. DCX deficiency shifted the distribution of CLASP2 proteins to the soma from the dendrites. In addition to CLASP2, dynein and its co-factor JIP3 were abnormally distributed in DCX-deficient neurons. The association between JIP3 and dynein was significantly increased in the absence of DCX. Downregulation of CLASP2 or JIP3 expression with specific shRNAs rescued the Golgi phenotype observed in DCX-deficient neurons. We conclude that DCX regulates the elongation of the Golgi apparatus into proximal dendrites through microtubule-associated proteins and motors.

双皮质素 ( DCX) 中的突变) 基因，编码微管结合蛋白，导致人类皮质畸形，包括无脑畸形和皮质下带异位。DCX 和双皮质素样激酶 1 (DCLK1)（一种功能冗余且结构相似的 DCX 同源物）的缺陷会减少神经突长度并增加直接由体细胞产生的初级神经突的数量。潜在的机制尚未完全了解。在这项研究中，在没有 DCX/DCLK1 的情况下，体细胞高尔基体向近端树突的伸长率显着降低，这与树突图案化有关。DCX 在 S47 或 S327 处的磷酸化参与此过程。DCX 缺陷使 CLASP2 蛋白的分布从树突转移到体细胞。除了 CLASP2，动力蛋白及其辅因子 JIP3 在 DCX 缺陷神经元中异常分布。在没有 DCX 的情况下，JIP3 和动力蛋白之间的关联显着增加。用特定 shRNA 下调 CLASP2 或 JIP3 表达挽救了在 DCX 缺陷神经元中观察到的高尔基体表型。我们得出结论，DCX 通过微管相关蛋白和马达调节高尔基体向近端树突的伸长。