Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, 604 Allison Road, Piscataway, NJ, USA.
Molecular Biosciences Graduate Program, Rutgers, The State University of New Jersey, 604 Allison Road, Piscataway, NJ, USA.
Cereb Cortex. 2019 Jul 5;29(7):2890-2903. doi: 10.1093/cercor/bhy155.
Higher brain function relies on proper development of the cerebral cortex, including correct positioning of neurons and dendrite morphology. Disruptions in these processes may result in various neurocognitive disorders. Mutations in the CPE gene, which encodes carboxypeptidase E (CPE), have been linked to depression and intellectual disability. However, it remains unclear whether CPE is involved in early brain development and in turn contributes to the pathophysiology of neurocognitive disorders. Here, we investigate the effects of CPE knockdown on early brain development and explore the functional significance of the interaction between CPE and its binding partner p150Glued. We demonstrate that CPE is required for cortical neuron migration and dendrite arborization. Furthermore, we show that expression of CPE-C10 redistributes p150Glued from the centrosome and that disruption of CPE interaction with p150Glued leads to abnormal neuronal migration and dendrite morphology, suggesting that a complex between CPE and p150Glued is necessary for proper neurodevelopment.
高级脑功能依赖于大脑皮层的正常发育，包括神经元的正确定位和树突形态。这些过程的紊乱可能导致各种神经认知障碍。编码羧肽酶 E (CPE) 的 CPE 基因突变与抑郁症和智力障碍有关。然而，目前尚不清楚 CPE 是否参与早期大脑发育，并进而导致神经认知障碍的病理生理学。在这里，我们研究了 CPE 敲低对早期大脑发育的影响，并探讨了 CPE 与其结合伴侣 p150Glued 之间相互作用的功能意义。我们证明 CPE 对于皮质神经元迁移和树突分支是必需的。此外，我们还表明 CPE-C10 的表达将 p150Glued 从中心体重新分配，并且 CPE 与 p150Glued 相互作用的破坏导致神经元迁移和树突形态异常，表明 CPE 和 p150Glued 之间的复合物对于正常的神经发育是必需的。
