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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Main Authors: Katarzyna O Rojek, Joanna Krzemień, Hubert Doleżyczek, Paweł M Boguszewski, Leszek Kaczmarek, Witold Konopka, Marcin Rylski, Jacek Jaworski, Lars Holmgren, Tomasz J Prószyński
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-05-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3000253
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author Katarzyna O Rojek
Joanna Krzemień
Hubert Doleżyczek
Paweł M Boguszewski
Leszek Kaczmarek
Witold Konopka
Marcin Rylski
Jacek Jaworski
Lars Holmgren
Tomasz J Prószyński
author_facet Katarzyna O Rojek
Joanna Krzemień
Hubert Doleżyczek
Paweł M Boguszewski
Leszek Kaczmarek
Witold Konopka
Marcin Rylski
Jacek Jaworski
Lars Holmgren
Tomasz J Prószyński
author_sort Katarzyna O Rojek
collection DOAJ
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.
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spelling doaj.art-f25e78cb23d540f684a9070631dea2442022-12-22T04:04:27ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-05-01175e300025310.1371/journal.pbio.3000253Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice.Katarzyna O RojekJoanna KrzemieńHubert DoleżyczekPaweł M BoguszewskiLeszek KaczmarekWitold KonopkaMarcin RylskiJacek JaworskiLars HolmgrenTomasz J PrószyńskiThe 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.https://doi.org/10.1371/journal.pbio.3000253
spellingShingle Katarzyna O Rojek
Joanna Krzemień
Hubert Doleżyczek
Paweł M Boguszewski
Leszek Kaczmarek
Witold Konopka
Marcin Rylski
Jacek Jaworski
Lars Holmgren
Tomasz J Prószyński
Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice.
PLoS Biology
title Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice.
title_full Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice.
title_fullStr Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice.
title_full_unstemmed Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice.
title_short Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice.
title_sort amot and yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice
url https://doi.org/10.1371/journal.pbio.3000253
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