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Usage Information

Huntingtin-associated protein 1 regulates postnatal neurogenesis and neurotrophin receptor sorting
Jianxing Xiang, … , Shi-Hua Li, Xiao-Jiang Li
Jianxing Xiang, … , Shi-Hua Li, Xiao-Jiang Li
Published December 20, 2013
Citation Information: J Clin Invest. 2014;124(1):85-98. https://doi.org/10.1172/JCI69206.
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Research Article Development

Huntingtin-associated protein 1 regulates postnatal neurogenesis and neurotrophin receptor sorting

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Abstract

Defective neurogenesis in the postnatal brain can lead to many neurological and psychiatric disorders, yet the mechanism behind postnatal neurogenesis remains to be investigated. Huntingtin-associated protein 1 (HAP1) participates in intracellular trafficking in neurons, and its absence leads to postnatal death in mice. Here, we used tamoxifen-induced (TM-induced) Cre recombination to deplete HAP1 in mice at different ages. We found that HAP1 reduction selectively affects survival and growth of postnatal mice, but not adults. Neurogenesis, but not gliogenesis, was affected in HAP1-null neurospheres and mouse brain. In the absence of HAP1, postnatal hypothalamic neurons exhibited reduced receptor tropomyosin-related kinase B (TRKB) levels and decreased survival. HAP1 stabilized the association of TRKB with the intracellular sorting protein sortilin, prevented TRKB degradation, and promoted its anterograde transport. Our findings indicate that intracellular sorting of neurotrophin receptors is critical for postnatal neurogenesis and could provide a therapeutic target for defective postnatal neurogenesis.

Authors

Jianxing Xiang, Hao Yang, Ting Zhao, Miao Sun, Xingshun Xu, Xin-Fu Zhou, Shi-Hua Li, Xiao-Jiang Li

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Usage data is cumulative from June 2024 through June 2025.

Usage JCI PMC
Text version 639 58
PDF 115 21
Figure 346 4
Supplemental data 38 0
Citation downloads 74 0
Totals 1,212 83
Total Views 1,295
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