Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice

Guoqing Sheng, Xingshun Xu, Yung Feng Lin, Chuan En Wang, Juan Rong, Dongmei Cheng, Junmin Peng, Xiaoyan Jiang, Shi Hua Li, Xiao Jiang Li

研究成果: 雜誌貢獻文章同行評審

59 引文 斯高帕斯(Scopus)


Joubert syndrome is an autosomal recessive disorder characterized by congenital malformation of the cerebellum and brainstem, with abnormal decussation in the brain. Mutations in the Abelson helper integration site 1 gene, which encodes the protein AHI1, have been shown to cause Joubert syndrome. In this study, we found that mouse Ahi1 formed a stable complex with huntingtin-associated protein 1 (Hap1), which is critical for neonatal development and involved in intracellular trafficking. Hap1-knockout mice showed significantly reduced Ahi1 levels, defective cerebellar development, and abnormal axonal decussation. Suppression of Ahi1 also decreased the level of Hap1; and truncated Ahi1, which corresponds to the mutations in Joubert syndrome, inhibited neurite outgrowth in neuronal culture. Reducing Hap1 expression suppressed the level and internalization of TrkB, a neurotrophic factor receptor that mediates neurogenesis and neuronal differentiation, which led to decreased TrkB signaling. These findings provide insight into the pathogenesis of Joubert syndrome and demonstrate the critical role of the Ahi1-Hap1 complex in early brain development.

頁(從 - 到)2785-2795
期刊Journal of Clinical Investigation
出版狀態已發佈 - 八月 1 2008

ASJC Scopus subject areas

  • Medicine(all)

指紋 深入研究「Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice」主題。共同形成了獨特的指紋。