title: Huntingtin-associated protein 1 regulates postnatal neurogenesis and neurotrophin receptor sorting.
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.forename: Jianxing
authors.initials: J
authors.lastname: Xiang
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Xingshun
authors.initials: X
authors.lastname: Xu
authors.forename: Xin-Fu
authors.initials: XF
authors.lastname: Zhou
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Li
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D008032:Limbic System / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis; D009928:Organ Specificity; D055550:Protein Stability; D021381:Protein Transport; D059748:Proteolysis; D020813:Receptor, trkB / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000502:physiology
chemical_list: C490758:Hap1 protein, mouse; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D020813:Receptor, trkB