The role of Amot and Yap1 in the regulation of dendritic tree morphogenesis and cerebellar functions

• Autorzy: Rojek K. , Krzemien J. , Dolezyczek H. , Rylski M. , Kaczmarek L. , Jaworski J. , Proszynski T.J.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: The Amot‑Yap1 complex plays a major role in the regulation of cell contact inhibition, cellular polarity and growth in many cell types. However, the function of the Amot and Hippo pathway transcription co‑activator Yap1 in the CNS remains unclear. Recent studies have demonstrated that, in mature hippocampal neurons, Amot localizes to dendritic spines where it associates with synaptic protein and regulates actin cytoskeleton. However, its function during neuronal development has not been studied. METHOD(S): Cultured primary neurons were used for RNAi experiments. For in vivo functional analysis, we used Amot and Yap1 conditional KO mice. For deletion in single sparse neurons, mice were injected with low doses of AAV‑CRE. For behavioral analysis, we used rotarod, catwalk, and foot fault tests. RESULTS: We demonstrate that Amot is a critical mediator of dendritogenesis 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. Conditional deletion of Amot or Yap1 in neurons leads to decreased Purkinje cell dendritic tree complexity, abnormal cerebellar morphology, and impaired motor coordination. The ability of Amot and Yap1 to regulate dendritic growth depends on regulation of S6 kinase activity and phosphorylation of S6 ribosomal protein. Hence, we suggest that Amot and Yap1 control dendritic tree morphogenesis through a cross‑talk with the PI3K/mTOR pathway, a known regulator of dendritogenesis. CONCLUSIONS: We identify a novel role for the scaffold protein Amot and the Hippo pathway transcription co‑activator Yap1 in dendritic morphogenesis. FINANCIAL SUPPORT: This research was supported by National Science Center grants 2012/05/E/ NZ3/00487 and 2015/19/N/NZ3/02346.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.LI-LII

Twórcy

autor

Rojek K.

• Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Krzemien J.

• Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Dolezyczek H.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Rylski M.

• Medical Center of Postgraduate Education, Warsaw, Poland

autor

Kaczmarek L.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Jaworski J.

• International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland

autor

Proszynski T.J.

• Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland