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

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.

Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons

“…Image-Pro Plus software with a neuronal tracer plug-in was used to determine neurite length, and ImageJ software with a Sholl plug-in was used for Sholl analysis of morphometric protrusions as previously described. 28 Briefly, images were randomly captured from over 40 neurons per group; each image was processed with the neuronal tracer plug-in; and a trace of all neurites (based on immunocytochemical analysis of GFP and tau-1 staining) on a confocal image was drawn manually.…”

The Effects of YAP and Its Related Mechanisms in Central Nervous System Diseases

“…Accordingly, the protein phosphatase 2A (PP2A) is regulated via TGF-β dephosphorylation and downregulation of p70s6k (Petritsch et al, 2000), which can also be phosphorylated by mTORC1 (Figure 2). Thus, the complex of mTORC1 and p70s6k, which is defined as one of the significant regulatory regulators of dendritic arbor development (Moser et al, 1997), is required for dendritic arbor development (Urbanska et al, 2012), including the width and number of dendritic branching point (Rojek et al, 2019). In addition to the above, the downstream effectors of mTORC2, which are essential to the growth of dendritic trees, are related to Akt.…”

“…After in-depth research, Hippo-YAP, which is defined as the core target of certain central nervous system diseases (Liu et al, 2017;Mueller et al, 2018;Rojek et al, 2019), usually transfers from the cytoplasm that binds to TEAD to the nucleus. The binding method is that the end of N YAP interacts with the spherical structure of the C-terminal of TEAD (four α-helices around β-sheets; Chen et al, 2010;Tian et al, 2010).…”

Behavioral Feeding Circuit: Dietary Fat-Induced Effects of Inflammatory Mediators in the Hypothalamus

“…Prenatal HFD exposure can impact DNA methylation of several genes related to dietary fat intake (62,63) as well as the levels and activity of several transcription factors that have been associated with brain development (64), such as transcriptional enhancer factor-1 (TEF-1), yes-associated protein-1 (YAP-1), and the family of peroxisome proliferatoractivated receptors (PPARs), that in turn effect the expression of some of the orexigenic neuropeptides (65)(66)(67)(68). The transcription factors TEF-1 and YAP-1 has been linked to prenatal HFD effects and plays a large role in organ formation and brain development during embryogenesis (69)(70)(71)(72), and activation of these transcription factors have been found to control neuronal proliferation and differentiation (73)(74)(75). Both TEF-1 and YAP-1 were inactivated or decreased during in utero HFD exposure and may promote increased neurogenesis events (65).…”