Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice
The angiomotin (Amot)-Yes-associated protein 1 (Yap1) complex plays a major role in regulating the inhibition of cell contact, cellular polarity, and cell growth in many cell types. However, the function of Amot and the Hippo pathway transcription coactivator Yap1 in the central nervous system remai...
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| creator | Rojek, Katarzyna O Krzemień, Joanna Doleżyczek, Hubert Boguszewski, Paweł M Kaczmarek, Leszek Konopka, Witold Rylski, Marcin Jaworski, Jacek Holmgren, Lars Prószyński, Tomasz J |
| description | The angiomotin (Amot)-Yes-associated protein 1 (Yap1) complex plays a major role in regulating the inhibition of cell contact, cellular polarity, and cell growth in many cell types. However, the function of Amot and the Hippo pathway transcription coactivator Yap1 in the central nervous system remains unclear. We found that Amot is a critical mediator of dendritic morphogenesis in cultured hippocampal cells and Purkinje cells in the brain. Amot function in developing neurons depends on interactions with Yap1, which is also indispensable for dendrite growth and arborization in vitro. The conditional deletion of Amot and Yap1 in neurons led to a decrease in the complexity of Purkinje cell dendritic trees, abnormal cerebellar morphology, and impairments in motor coordination. Our results indicate that the function of Amot and Yap1 in dendrite growth does not rely on interactions with TEA domain (TEAD) transcription factors or the expression of Hippo pathway-dependent genes. Instead, Amot and Yap1 regulate dendrite development by affecting the phosphorylation of S6 kinase and its target S6 ribosomal protein. |
| doi_str_mv | 10.1371/journal.pbio.3000253 |
| format | Article |
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However, the function of Amot and the Hippo pathway transcription coactivator Yap1 in the central nervous system remains unclear. We found that Amot is a critical mediator of dendritic morphogenesis in cultured hippocampal cells and Purkinje cells in the brain. Amot function in developing neurons depends on interactions with Yap1, which is also indispensable for dendrite growth and arborization in vitro. The conditional deletion of Amot and Yap1 in neurons led to a decrease in the complexity of Purkinje cell dendritic trees, abnormal cerebellar morphology, and impairments in motor coordination. Our results indicate that the function of Amot and Yap1 in dendrite growth does not rely on interactions with TEA domain (TEAD) transcription factors or the expression of Hippo pathway-dependent genes. Instead, Amot and Yap1 regulate dendrite development by affecting the phosphorylation of S6 kinase and its target S6 ribosomal protein.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.3000253</identifier><identifier>PMID: 31042703</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptor Proteins, Signal Transducing - metabolism ; Analysis ; Animal locomotion ; Animals ; Autism ; Binding proteins ; Biology ; Biology and Life Sciences ; Brain ; Cell adhesion & migration ; Cell Cycle Proteins - metabolism ; Cell growth ; Central nervous system ; Cerebellum ; Clonal deletion ; Complexity ; Control ; Coordination ; Cytology ; Dendrites - metabolism ; Dendritic branching ; Dendritic cells ; Dendritic structure ; Gene expression ; Hippocampus ; Hippocampus - cytology ; Influence ; Integrases - metabolism ; Intercellular Signaling Peptides and Proteins - metabolism ; Kinases ; Localization ; Locomotion - physiology ; Mammals ; Medicine and Health Sciences ; Mice, Inbred C57BL ; Microfilament Proteins - metabolism ; Morphogenesis ; Morphology ; Motor Activity ; Neurons ; Phosphorylation ; Polarity ; Protein Binding ; Proteins ; Purkinje cells ; Purkinje Cells - metabolism ; Rats, Wistar ; Ribosomal Protein S6 - metabolism ; Transcription factors ; Trees ; Yes-associated protein</subject><ispartof>PLoS biology, 2019-05, Vol.17 (5), p.e3000253-e3000253</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Rojek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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However, the function of Amot and the Hippo pathway transcription coactivator Yap1 in the central nervous system remains unclear. We found that Amot is a critical mediator of dendritic morphogenesis in cultured hippocampal cells and Purkinje cells in the brain. Amot function in developing neurons depends on interactions with Yap1, which is also indispensable for dendrite growth and arborization in vitro. The conditional deletion of Amot and Yap1 in neurons led to a decrease in the complexity of Purkinje cell dendritic trees, abnormal cerebellar morphology, and impairments in motor coordination. Our results indicate that the function of Amot and Yap1 in dendrite growth does not rely on interactions with TEA domain (TEAD) transcription factors or the expression of Hippo pathway-dependent genes. 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| fulltext | fulltext |
| identifier | ISSN: 1545-7885 |
| ispartof | PLoS biology, 2019-05, Vol.17 (5), p.e3000253-e3000253 |
| issn | 1545-7885 1544-9173 1545-7885 |
| language | eng |
| recordid | cdi_plos_journals_2249987948 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; SWEPUB Freely available online; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adaptor Proteins, Signal Transducing - metabolism Analysis Animal locomotion Animals Autism Binding proteins Biology Biology and Life Sciences Brain Cell adhesion & migration Cell Cycle Proteins - metabolism Cell growth Central nervous system Cerebellum Clonal deletion Complexity Control Coordination Cytology Dendrites - metabolism Dendritic branching Dendritic cells Dendritic structure Gene expression Hippocampus Hippocampus - cytology Influence Integrases - metabolism Intercellular Signaling Peptides and Proteins - metabolism Kinases Localization Locomotion - physiology Mammals Medicine and Health Sciences Mice, Inbred C57BL Microfilament Proteins - metabolism Morphogenesis Morphology Motor Activity Neurons Phosphorylation Polarity Protein Binding Proteins Purkinje cells Purkinje Cells - metabolism Rats, Wistar Ribosomal Protein S6 - metabolism Transcription factors Trees Yes-associated protein |
| title | Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T00%3A02%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Amot%20and%20Yap1%20regulate%20neuronal%20dendritic%20tree%20complexity%20and%20locomotor%20coordination%20in%20mice&rft.jtitle=PLoS%20biology&rft.au=Rojek,%20Katarzyna%20O&rft.date=2019-05-01&rft.volume=17&rft.issue=5&rft.spage=e3000253&rft.epage=e3000253&rft.pages=e3000253-e3000253&rft.issn=1545-7885&rft.eissn=1545-7885&rft_id=info:doi/10.1371/journal.pbio.3000253&rft_dat=%3Cgale_plos_%3EA587702575%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2249987948&rft_id=info:pmid/31042703&rft_galeid=A587702575&rft_doaj_id=oai_doaj_org_article_f25e78cb23d540f684a9070631dea244&rfr_iscdi=true |