Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons

Wu, Yu; Lv, Xiaoshu; Wang, Haiting; Qian, Kai; Ding, Jin-Jun; Wang, Jiejie; Hua, Shushan; Sun, Tian-Cheng; Zhou, Yixi; Yu, Lina; Qiu, Shuang

doi:10.1093/jmcb/mjaa058

Cited by 5 publications

(2 citation statements)

References 52 publications

(64 reference statements)

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“…In the present study, we found that inhibiting the expression of KLK6 led to the upregulation of Appl2, Nav2, and Nrn1 expression in neurons, which may be the potential mechanism of KLK6 inhibition to protect neuronal synaptic structures from damage. Appls are multifunctional adaptor proteins; Appl2 is an isoform of Appl1 that mediates the PI3K/Akt cascade to promote cortical neuronal survival (Wu et al 2020) and also contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling (Liu et al 2017). Thus, it is reasonable that Appl2 is involved in siRNA-KLK6mediated synaptic structural recovery.…”

Section: Discussionmentioning

confidence: 99%

Proteomic and Functional Analyses Reveal That Kallikrein 6 Enhances Communicating Hydrocephalus by Injuring Neuronal Synapses

Yuan¹,

Zou²,

Yang³

et al. 2021

Preprint

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Communicating hydrocephalus (CH) is a common neurological disorder caused by a blockage of cerebrospinal fluid. In this study, we aimed to explore the potential molecular mechanism underlying CH development. Quantitative proteomic analysis was performed to screen the differentially expressed proteins (DEPs) between patients with and without CH. A CH rat model was verified by Hoechst staining, and the co-localization of the target protein and neuron was detected using immunofluorescence staining. Loss-of-function experiments were performed to examine the effect of KLK6 on the synapse structure. A total of 11 DEPs were identified, and kallikrein 6 (KLK6) expression was found to be significantly upregulated in patients with CH compared with that in patients without CH. The CH rat model was successfully constructed, and KLK6 was found to be co-localized with neuronal nuclei in brain tissue. The expression level of KLK6 in the CH group was higher than that in the control group. After interference of KLK6 expression, the expression levels of synapsin-1 and PSD95 in neuronal cells were increased, and the length, number, and structure of synapses were significantly improved. The transcriptome profile (PRJNA719985) after interference of KLK6 expression was obtained, and 5,681 differentially expressed genes (DEGs) were identified. The upregulated DEGs of Appl2, Nav2, and Nrn1 may be involved in the recovery of synaptic structures after interference of KLK6 expression. Collectively, KLK6 participates in the development of CH and might provide a new target for CH treatment.

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Section: Discussionmentioning

confidence: 99%

Proteomic and Functional Analyses Reveal That Kallikrein 6 Enhances Communicating Hydrocephalus by Injuring Neuronal Synapses

Yuan¹,

Zou²,

Yang³

et al. 2021

Preprint

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“…In parallel, dendritic spine-located APPL1 senses synaptic activity and is translocated to the nucleus upon neuronal activation, where it facilitates transcription necessary for late-phase LTP maintenance. Blocking APPL1 activity impairs late LTP but not LTP induction nor early LTP [ 62 ].…”

Section: Central Adiponectin Signaling Regulates Cellular Metabolism ...mentioning

confidence: 99%

Central Adiponectin Signaling – A Metabolic Regulator in Support of Brain Plasticity

Formolo

Cheng

et al. 2022

BPL

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Brain plasticity and metabolism are tightly connected by a constant influx of peripheral glucose to the central nervous system in order to meet the high metabolic demands imposed by neuronal activity. Metabolic disturbances highly affect neuronal plasticity, which underlies the prevalent comorbidity between metabolic disorders, cognitive impairment, and mood dysfunction. Effective pro-cognitive and neuropsychiatric interventions, therefore, should consider the metabolic aspect of brain plasticity to achieve high effectiveness. The adipocyte-secreted hormone, adiponectin, is a metabolic regulator that crosses the blood-brain barrier and modulates neuronal activity in several brain regions, where it exerts neurotrophic and neuroprotective properties. Moreover, adiponectin has been shown to improve neuronal metabolism in different animal models, including obesity, diabetes, and Alzheimer’s disease. Here, we aim at linking the adiponectin’s neurotrophic and neuroprotective properties with its main role as a metabolic regulator and to summarize the possible mechanisms of action on improving brain plasticity via its role in regulating the intracellular energetic activity. Such properties suggest adiponectin signaling as a potential target to counteract the central metabolic disturbances and impaired neuronal plasticity underlying many neuropsychiatric disorders.

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Protein Transport from Synapse-to-Nucleus and the Regulation of Gene Expression

Karpova,

Andres-Alonso,

Grochowska

et al. 2024

Transcriptional Regulation by Neuronal Activity

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Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons

Cited by 5 publications

References 52 publications

Proteomic and Functional Analyses Reveal That Kallikrein 6 Enhances Communicating Hydrocephalus by Injuring Neuronal Synapses

Proteomic and Functional Analyses Reveal That Kallikrein 6 Enhances Communicating Hydrocephalus by Injuring Neuronal Synapses

Central Adiponectin Signaling – A Metabolic Regulator in Support of Brain Plasticity

Protein Transport from Synapse-to-Nucleus and the Regulation of Gene Expression

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