Tumor suppressor protein CYLD regulates morphogenesis of dendrites and spines

被引:13
|
作者
Li, Jun [1 ]
Sekine-Aizawa, Yoko [1 ]
Ebrahimi, Saman [1 ]
Tanaka, Shinji [1 ]
Okabe, Shigeo [1 ]
机构
[1] Univ Tokyo, Grad Sch Med, Dept Cellular Neurobiol, Tokyo, Japan
关键词
dendritic morphogenesis; hippocampal neuron; microtubule; spine formation; tubulin acetylation; NF-KAPPA-B; POSTSYNAPTIC DENSITY; PROTEOMIC ANALYSIS; RAT FOREBRAIN; DYNAMICS; ACTIN; PLASTICITY; MICROTUBULES; CYTOSKELETON; ADF/COFILIN;
D O I
10.1111/ejn.14421
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cylindromatosis tumor suppressor protein (CYLD) was initially identified as a tumor suppressor deubiquitylating protein in familial cylindromatosis patients. Proteomic analyses using rodent brain samples revealed enrichment of CYLD in purified postsynaptic density fractions. Here, we report that CYLD regulates dendritic growth and postsynaptic differentiation in mouse hippocampal neurons. CYLD showed diffuse localization in rapidly growing dendrites, but was gradually concentrated in spines. Overexpression and knockdown of CYLD in the early stage of cultured neurons demonstrated that CYLD positively regulated dendritic growth. Phenotypes in dendritic morphogenesis induced by CYLD overexpression and knockdown could be reversed by manipulation of the critical acetylation site of alpha-tubulin, suggesting tubulin acetylation is a downstream pathway of CYLD-dependent dendritic growth. Overexpression and knockdown of CYLD in the later stage of cultured neurons revealed that CYLD promoted formation of postsynaptic spines. Influence of CYLD on spines was not affected by co-expression of acetylation mutant forms of alpha-tubulin, indicating that CYLD regulates dendritic growth and spine formation through different molecular mechanisms. Analyses with the truncated and mutated forms of CYLD demonstrated that the first microtubule-binding domain of CYLD was critical for spine formation. These results suggest important roles of CYLD in sequential promotion of dendritic growth and postsynaptic spine maturation.
引用
收藏
页码:2722 / 2739
页数:18
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