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.
机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Lim, Jae Hyang
Stirling, Brigid
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Stirling, Brigid
Derry, Jonathan
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Derry, Jonathan
Koga, Tomoaki
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Koga, Tomoaki
Jono, Hirofumi
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Jono, Hirofumi
Woo, Chang-Hoon
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Woo, Chang-Hoon
Xu, Haodong
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Xu, Haodong
Bourne, Patricia
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Bourne, Patricia
Ha, Un-Hwan
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Ha, Un-Hwan
Ishinaga, Hajime
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Ishinaga, Hajime
Xu, Haidong
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Xu, Haidong
Andalibi, Ali
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Andalibi, Ali
Feng, Xin-Hua
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Feng, Xin-Hua
Zhu, Hongguang
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Zhu, Hongguang
Huang, Yuxian
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Huang, Yuxian
Zhang, Wenhong
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Zhang, Wenhong
Weng, Xinhua
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Weng, Xinhua
Yan, Chen
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Yan, Chen
Yin, Zhinan
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Yin, Zhinan
Briles, David E.
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Briles, David E.
Davis, Roger J.
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Davis, Roger J.
Flavell, Richard A.
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机构:Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Flavell, Richard A.
Li, Jian-Dong
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Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USAUniv Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
机构:
Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R ChinaShandong Normal Univ, Coll Life Sci, Inst Biomed Sci, Key Lab Anim Resistance Biol Shandong Prov, Jinan 250014, Shandong, Peoples R China
Yang, Yunfan
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Gao, Siqi
Song, Ting
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Shandong Normal Univ, Coll Life Sci, Inst Biomed Sci, Key Lab Anim Resistance Biol Shandong Prov, Jinan 250014, Shandong, Peoples R ChinaShandong Normal Univ, Coll Life Sci, Inst Biomed Sci, Key Lab Anim Resistance Biol Shandong Prov, Jinan 250014, Shandong, Peoples R China
Song, Ting
Wu, Yuhan
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Shandong Normal Univ, Coll Life Sci, Inst Biomed Sci, Key Lab Anim Resistance Biol Shandong Prov, Jinan 250014, Shandong, Peoples R ChinaShandong Normal Univ, Coll Life Sci, Inst Biomed Sci, Key Lab Anim Resistance Biol Shandong Prov, Jinan 250014, Shandong, Peoples R China
Wu, Yuhan
Li, Dengwen
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Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R ChinaShandong Normal Univ, Coll Life Sci, Inst Biomed Sci, Key Lab Anim Resistance Biol Shandong Prov, Jinan 250014, Shandong, Peoples R China
Li, Dengwen
Liu, Min
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Shandong Normal Univ, Coll Life Sci, Inst Biomed Sci, Key Lab Anim Resistance Biol Shandong Prov, Jinan 250014, Shandong, Peoples R ChinaShandong Normal Univ, Coll Life Sci, Inst Biomed Sci, Key Lab Anim Resistance Biol Shandong Prov, Jinan 250014, Shandong, Peoples R China
机构:
Key Laboratory of Animal Resistance Biology of Shandong Province,Institute of Biomedical Sciences,College of Life Sciences,Shandong Normal UniversityKey Laboratory of Animal Resistance Biology of Shandong Province,Institute of Biomedical Sciences,College of Life Sciences,Shandong Normal University
Wei Xie
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Yunfan Yang
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Siqi Gao
Ting Song
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Key Laboratory of Animal Resistance Biology of Shandong Province,Institute of Biomedical Sciences,College of Life Sciences,Shandong Normal UniversityKey Laboratory of Animal Resistance Biology of Shandong Province,Institute of Biomedical Sciences,College of Life Sciences,Shandong Normal University
Ting Song
Yuhan Wu
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Key Laboratory of Animal Resistance Biology of Shandong Province,Institute of Biomedical Sciences,College of Life Sciences,Shandong Normal UniversityKey Laboratory of Animal Resistance Biology of Shandong Province,Institute of Biomedical Sciences,College of Life Sciences,Shandong Normal University
Yuhan Wu
Dengwen Li
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机构:
State Key Laboratory of Medicinal Chemical Biology,College of Life Sciences,Nankai UniversityKey Laboratory of Animal Resistance Biology of Shandong Province,Institute of Biomedical Sciences,College of Life Sciences,Shandong Normal University
机构:
Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USAPenn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA
Reiley, W
Zhang, MY
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Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USAPenn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA
Zhang, MY
Sun, SC
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Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USAPenn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA