Xing Zhen-Kai, Zhang Lu-Qing, Zhang Yu, Sun Xue, Sun Xiao-Lin, Yu Hua-Li, Zheng Yao-Wu, He Zi-Xuan, Zhu Xiao-Juan
Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
Front Cell Neurosci. 2020 Feb 19;14:29. doi: 10.3389/fncel.2020.00029. eCollection 2020.
Axonal development is essential to the establishment of neuronal morphology and circuitry, although the mechanisms underlying axonal outgrowth during the early developmental stages remain unclear. Here, we showed that the conserved disco-interacting protein B (DIP2B) which consists of a DMAP1 domain and a crotonobetaine/carnitine CoA ligase (Caic) domain, is highly expressed in the excitatory neurons of the hippocampus. DIP2B knockout led to excessive axonal outgrowth but not polarity at an early developmental stage. Furthermore, the loss of DIP2B inhibited synaptic transmission for both spontaneous and rapid release in cultured hippocampal neurons. Interestingly, DIP2B function during axonal outgrowth requires tubulin acetylation. These findings reveal a new conserved regulator of neuronal morphology and provide a novel intervention mechanism for neurocognitive disorders.
轴突发育对于神经元形态和神经回路的建立至关重要，尽管早期发育阶段轴突生长的潜在机制仍不清楚。在这里，我们表明，由DMAP1结构域和巴豆甜菜碱/肉碱辅酶A连接酶（Caic）结构域组成的保守的盘状相互作用蛋白B（DIP2B）在海马体的兴奋性神经元中高度表达。DIP2B基因敲除导致在早期发育阶段轴突过度生长，但不影响极性。此外，DIP2B的缺失抑制了培养的海马神经元中自发和快速释放的突触传递。有趣的是，轴突生长过程中DIP2B的功能需要微管蛋白乙酰化。这些发现揭示了一种新的神经元形态保守调节因子，并为神经认知障碍提供了一种新的干预机制。
