Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice

PLoS Biol. 2019 May 1;17(5):e3000253. doi: 10.1371/journal.pbio.3000253. eCollection 2019 May.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Cycle Proteins / metabolism*
  • Dendrites / metabolism*
  • Hippocampus / cytology
  • Integrases / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Locomotion / physiology*
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism*
  • Morphogenesis
  • Motor Activity
  • Phosphorylation
  • Protein Binding
  • Purkinje Cells / metabolism
  • Rats, Wistar
  • Ribosomal Protein S6 / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Amot protein, mouse
  • Cell Cycle Proteins
  • Intercellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Ribosomal Protein S6
  • Yap1 protein, mouse
  • Cre recombinase
  • Integrases

Grant support

Sonata-Bis grant no. 2012/05/E/NZ3/00487 from the Polish National Science Center (https://ncn.gov.pl/?language=en) was awarded to TJP. Preludium grant no. 2015/19/N/NZ3/02346 from the Polish National Science Center (https://ncn.gov.pl/?language=en) was awarded to KOR. Grants from the Swedish Cancer Society (https://www.cancerfonden.se/om-cancerfonden/about-the-swedish-cancer-society), Swedish Research Council (https://www.vr.se/english.html), and the Cancer Society of Stockholm (https://www.uicc.org/membership/cancer-society-stockholm) were awarded to LH. The "ANIMOD" project is carried out within the Team Tech Core Facility Plus program of the Foundation for Polish Science cofinanced by the European Union under the European Regional Development Fund to WK and PMB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.