Role of HAUS7 as a DOCK3 binding partner in facilitating axon regeneration

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-07-25 DOI:10.1126/sciadv.adq7105

Naoki Kiyota, Youichi Shinozaki, Xiaoli Guo, Atsuko Kimura, Kazuto Kawamura, Euido Nishijima, Sari Honda, Chikako Harada, Toru Nakazawa, Kazuhiko Namekata, Takayuki Harada

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Abstract

The molecular mechanisms involved in reconstructing the eye-to-brain connection and functional recovery following optic nerve damage remain unclear. This study revealed that HAUS augmin-like complex subunit 7 (HAUS7) is a molecule that binds to dedicator of cytokinesis 3 (DOCK3), a regulator of neurotrophic factor signaling and axon regeneration. We observed a distribution pattern of HAUS7 expression, suggesting that neuronal HAUS7 is transported from the cell body to the growth cone under the control of DOCK3. In addition, phosphorylation of DOCK3 at Y562 by tropomyosin receptor kinase B signaling leads to the dissociation of HAUS7, which is considered an important step for microtubule assembly. Deletion of Haus7 in mice significantly reduced microtubule formation and axon regeneration following optic nerve crush (ONC). Transcriptome analysis suggested that HAUS7 levels decrease in glaucoma and after the ONC, while retinal ganglion cells actively regenerating their axons express high levels of HAUS7. In summary, HAUS7 is a binding partner of DOCK3 necessary for axon elongation.

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HAUS7作为DOCK3结合伙伴在促进轴突再生中的作用

视神经损伤后重建眼脑连接和功能恢复的分子机制尚不清楚。该研究表明，HAUS augin -样复合体亚单位7 （HAUS7）是一种结合细胞分裂奉献子3 （DOCK3）的分子，DOCK3是神经营养因子信号传导和轴突再生的调节因子。我们观察到HAUS7的表达分布模式，表明神经元HAUS7在DOCK3的控制下从细胞体转运到生长锥。此外，原肌球蛋白受体激酶B信号通路磷酸化DOCK3的Y562位点导致HAUS7的解离，这被认为是微管组装的重要步骤。小鼠中Haus7的缺失显著减少视神经挤压（ONC）后的微管形成和轴突再生。转录组分析表明，HAUS7水平在青光眼和ONC后下降，而视网膜神经节细胞轴突再生活跃表达高水平的HAUS7。综上所述，HAUS7是轴突伸长所必需的DOCK3的结合伴侣。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.