A neuroprotective role of Ufmylation through Atg9 in the aging brain of Drosophila

Li, Huifang; Yu, Zhenghong; Niu, Zikang; Cheng, Yun; Wei, Zhenhao; Cai, Yafei; Ma, Fei; Hu, Lanxin; Zhu, Jiejie; Zhang, Wei

doi:10.1007/s00018-023-04778-9

Cited by 6 publications

(2 citation statements)

References 69 publications

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“…E3 UFM1-protein ligase mediates ufmylation of target proteins. Ufmylation is a recently identified small ubiquitin-like modification, whose biological function and relevant cellular targets are poorly understood 55 .…”

Section: Resultsmentioning

confidence: 99%

In vivo identification of Drosophila rhodopsin interaction partners by biotin proximity labeling

Feizy,

Leuchtenberg,

Steiner

et al. 2024

Sci Rep

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Proteins exert their function through protein–protein interactions. In Drosophila, G protein-coupled receptors like rhodopsin (Rh1) interact with a G protein to activate visual signal transduction and with arrestins to terminate activation. Also, membrane proteins like Rh1 engage in protein–protein interactions during folding within the endoplasmic reticulum, during their vesicular transport and upon removal from the cell surface and degradation. Here, we expressed a Rh1-TurboID fusion protein (Rh1::TbID) in Drosophila photoreceptors to identify in vivo Rh1 interaction partners by biotin proximity labeling. We show that Rh1::TbID forms a functional rhodopsin that mediates biotinylation of arrestin 2 in conditions where arrestin 2 interacts with rhodopsin. We also observed biotinylation of Rh1::TbID and native Rh1 as well as of most visual signal transduction proteins. These findings indicate that the signaling components in the rhabdomere approach rhodopsin closely, within a range of ca. 10 nm. Furthermore, we have detected proteins engaged in the maturation of rhodopsin and elements responsible for the trafficking of membrane proteins, resembling potential interaction partners of Rh1. Among these are chaperons of the endoplasmic reticulum, proteins involved in Clathrin-mediated endocytosis as well as previously unnoticed contributors to rhodopsin transportation, such as Rab32, Vap33, or PIP82.

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Section: Resultsmentioning

confidence: 99%

In vivo identification of Drosophila rhodopsin interaction partners by biotin proximity labeling

Feizy,

Leuchtenberg,

Steiner

et al. 2024

Sci Rep

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show abstract

“…The mTOR, composed of two complexes (mTORC1 and mTORC2), regulates protein translation and cell growth by responding to a variety of environmental variables, such as growth factors, nutrition and energy [ 55 ]; phosphatidylinositol 3-kinase (PI3K)/Akt (Protein Kinase B) and AMPK are the major regulators of mTOR [ 56 ]. In agreement with the findings of the present study, several studies have found a significant effect of Al exposure on the protein expression of PI3K, Akt and mTOR, which are involved in neuronal plasticity [ 57 ], implying that increased Al exposure in the brain is accompanied by decreased expression of the mTOR signaling pathway, leading to neuronal damage and cognitive decline [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Dapagliflozin Ameliorates Cognitive Impairment in Aluminum-Chloride-Induced Alzheimer’s Disease via Modulation of AMPK/mTOR, Oxidative Stress and Glucose Metabolism

et al. 2023

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Alzheimer’s disease (AD) is a progressive neurological illness characterized by memory loss and cognitive deterioration. Dapagliflozin was suggested to attenuate the memory impairment associated with AD; however, its mechanisms were not fully elucidated. This study aims to examine the possible mechanisms of the neuroprotective effects of dapagliflozin against aluminum chloride (AlCl3)-induced AD. Rats were distributed into four groups: group 1 received saline, group 2 received AlCl3 (70 mg/kg) daily for 9 weeks, and groups 3 and 4 were administered AlCl3 (70 mg/kg) daily for 5 weeks. Dapagliflozin (1 mg/kg) and dapagliflozin (5 mg/kg) were then given daily with AlCl3 for another 4 weeks. Two behavioral experiments were performed: the Morris Water Maze (MWM) and the Y-maze spontaneous alternation (Y-maze) task. Histopathological alterations in the brain, as well as changes in acetylcholinesterase (AChE) and amyloid β (Aβ) peptide activities and oxidative stress (OS) markers, were all evaluated. A western blot analysis was used for the detection of phosphorylated 5’ AMP-activated protein kinase (p-AMPK), phosphorylated mammalian target of Rapamycin (p-mTOR) and heme oxygenase-1 (HO-1). Tissue samples were collected for the isolation of glucose transporters (GLUTs) and glycolytic enzymes using PCR analysis, and brain glucose levels were also measured. The current data demonstrate that dapagliflozin represents a possible approach to combat AlCl3-induced AD in rats through inhibiting oxidative stress, enhancing glucose metabolism and activating AMPK signaling.

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UFMylation: An integral post-translational modification for the regulation of proteostasis and cellular functions

Wang,

Lv,

et al. 2024

Pharmacology & Therapeutics

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A neuroprotective role of Ufmylation through Atg9 in the aging brain of Drosophila

Cited by 6 publications

References 69 publications

In vivo identification of Drosophila rhodopsin interaction partners by biotin proximity labeling

In vivo identification of Drosophila rhodopsin interaction partners by biotin proximity labeling

Dapagliflozin Ameliorates Cognitive Impairment in Aluminum-Chloride-Induced Alzheimer’s Disease via Modulation of AMPK/mTOR, Oxidative Stress and Glucose Metabolism

UFMylation: An integral post-translational modification for the regulation of proteostasis and cellular functions

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