Abstract
PHRF1 is involved in transforming growth factor β (TGF-β) signaling to constrain the formation of acute promyelocytic leukemia (APL) in mouse APL models. PHRF1 also participates in modulating non-homologous end-joining. However, the role of PHRF1 in mammalian dendrite architecture and synaptic plasticity is unclear. Here, we investigated the role of PHRF1 in dendritic formation in the murine hippocampus using Camk2a promoter driven-iCre recombinase to conduct a PHRF1 conditional knockout, namely PHRF1Δ/Δ, in the forebrain region. PHRF1Δ/Δ mice developed normally, but exhibited anxiety-like behaviors and displayed defective spatial memory. Alterations of dendritic complexity in apical and basal dendrites of pyramidal neurons were noticed in PHRF1Δ/Δ mutants. Furthermore, electrical stimulation in the hippocampal CA1 region after the TGF-β1 treatment showed a reduced synaptic plasticity in PHRF1Δ/Δ mice. Immunoblotting analysis indicated that PHRF1 ablation affected the TGF-β signaling. Collectively, our results demonstrate that PHRF1 is important for the dendritic architecture and required for spatial memory formation in the hippocampus.
Highlights
PHRF1 is involved in transforming growth factor β (TGF-β) signaling to constrain the formation of acute promyelocytic leukemia (APL) in mouse APL models
PHRF1 mediates the degradation of the TG interacting factor (TGIF) to promote the function of the cytoplasmic variant of the promyelocytic leukemia protein in TGF-β signalling[10]
Immunoblotting analysis confirmed a significant reduction of PHRF1 in the hippocampal extracts prepared from adult PHRF1Δ/Δ mice, compared with PHRF1fl/fl controls (Fig. 1b). PHRF1Δ/Δ mice were viable with no noticeable apparent defects
Summary
PHRF1 is involved in transforming growth factor β (TGF-β) signaling to constrain the formation of acute promyelocytic leukemia (APL) in mouse APL models. In addition to the tri-synaptic loop, the critical functions of pyramidal neurons in the hippocampal CA1 region are the way they respond to surrounding stimuli and produce excitatory outputs to its postsynaptic targets. This process of information integration is largely dependent on the helm of dendritic structure and function[3]. Many factors have been found to participate in learning and memory in the hippocampal circuits, the role of PHRF1 in the hippocampal dendritic architecture and synaptic plasticity remains unclear. In P HRF1Δ/Δ mice, the complexity of dendritic architectures in the hippocampal neurons was altered, while hippocampus-mediated spatial learning and memory was impaired. These results lead us to conclude that PHRF1 is important for the formation of hippocampal dendritic structure and memory formation
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