The mechanistic link between Arc/Arg3.1 expression and AMPA receptor endocytosis

Wall, Mark J.; Corrêa, Sônia A.L.

doi:10.1016/j.semcdb.2017.09.005

Cited by 36 publications

(37 citation statements)

References 87 publications

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“…Accordingly, considering the role of Arc/Arg3.1 in synaptic plasticity regulation, its increased expression suggests dynamic homeostatic compensation for VC neuronal network stabilisation after overactivation ( Fig. 11b) (Rial Verde et al 2006;Bramham et al 2008;Wall and Corrêa 2018). Our results from all neuronal markers analysed in the VC indicated an increase in GAD67 immunostaining restricted to VC1, with no overall changes in gene expression in the VC.…”

Section: Visual Cortex Plastic Reactionmentioning

confidence: 61%

Cross-modal reaction of auditory and visual cortices after long-term bilateral hearing deprivation in the rat

et al. 2019

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Visual cortex (VC) over-activation analysed by evoked responses has been demonstrated in congenital deafness and after longterm acquired hearing loss in humans. However, permanent hearing deprivation has not yet been explored in animal models. Thus, the present study aimed to examine functional and molecular changes underlying the visual and auditory cross-modal reaction. For such purpose, we analysed cortical visual evoked potentials (VEPs) and the gene expression (RT-qPCR) of a set of markers for neuronal activation (c-Fos) and activity-dependent homeostatic compensation (Arc/Arg3.1). To determine the state of excitation and inhibition, we performed RT-qPCR and quantitative immunocytochemistry for excitatory (receptor subunits GluA2/3) and inhibitory (GABAA-α1, GABAB-R2, GAD65/67 and parvalbumin-PV) markers. VC over-activation was demonstrated by a significant increase in VEPs wave N1 and by up-regulation of the activity-dependent early genes c-Fos and Arc/Arg3.1 (thus confirming, by RT-qPCR, our previously published immunocytochemical results). GluA2 gene and protein expression were significantly increased in the auditory cortex (AC), particularly in layers 2/3 pyramidal neurons, but inhibitory markers (GAD65/67 and PV-GABA interneurons) were also significantly upregulated in the AC, indicating a concurrent increase in inhibition. Therefore, after permanent hearing loss in the rat, the VC is not only over-activated but also potentially balanced by homeostatic regulation, while excitatory and inhibitory markers remain imbalanced in the AC, most likely resulting from changes in horizontal intermodal regulation.

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Section: Visual Cortex Plastic Reactionmentioning

confidence: 61%

Cross-modal reaction of auditory and visual cortices after long-term bilateral hearing deprivation in the rat

et al. 2019

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“…Arc/Arg3.1 accelerates AMPA receptor endocytosis through interaction with AP-2, endophilin-3 and dynamin-2 16,18 following mGluR activation 37 . In the Arc knock-in mouse (ArcKR), lysines 268 and 269 in the Arc protein are mutated to arginine, which interferes with Arc ubiquitination.…”

Section: Representative Resultsmentioning

confidence: 99%

“…, Arc is known to mediate metabotropic glutamate receptor (mGluR)-dependent LTD by promoting AMPA receptor endocytosis through its binding partners, which include the endocytic proteins AP-2, endophilin-3, and dynamin-2 16,17,18,19 , at clathrin-coated pits 20,21 . Internalized AMPA receptors can either be recycled back to the plasma membrane or earmarked for degradation 22,23 .…”

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confidence: 99%

A High-content Assay for Monitoring AMPA Receptor Trafficking

Ghane

Yakout

Mabb

2019

JoVE

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Postsynaptic trafficking of receptors to and from the cell surface is an important mechanism by which neurons modulate their responsiveness to different stimuli. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which are responsible for fast excitatory synaptic transmission in neurons, are trafficked to and from the postsynaptic surface to dynamically alter neuronal excitability. AMPA receptor trafficking is essential for synaptic plasticity and can be disrupted in neurological disease. However, prevalent approaches for quantifying receptor trafficking ignore entire receptor pools, are overly time-and labor-intensive, or potentially disrupt normal trafficking mechanisms and therefore complicate the interpretation of resulting data. We present a high-content assay for the quantification of both surface and internal AMPA receptor populations in cultured primary hippocampal neurons using dual fluorescent immunolabeling and a near-infrared fluorescent 96-well microplate scanner. This approach facilitates the rapid screening of bulk internalized and surface receptor densities while minimizing sample material. However, our method has limitations in obtaining single-cell resolution or conducting live cell imaging. Finally, this protocol may be amenable to other receptors and different cell types, provided proper adjustments and optimization. Video Link The video component of this article can be found at https://www.jove.com/video/59048/ 28 , renders the channel pore impermeable to calcium 29 , further implicating subunit-specific trafficking as a key mediator of neuronal homeostasis and plasticity. Interestingly, disruption of ubiquitin-dependent Arc degradation has been shown to increase GluA1 endocytosis and increase the surface expression of GluA2 subunit-containing AMPA receptors after induction of mGluR-LTD with the selective

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“…How might Arc1 promote IIS-pathway activity? Mammalian Arc modulates synaptic plasticity in part by enhancing the endocytosis, and consequently reducing the membrane availability, of AMPA receptors (Chowdhury et al, 2006;DaSilva et al, 2016;Wall and Corrêa, 2018). Although it has not been shown for Arc1, this molecular function suggests that Arc proteins may have the ability to regulate the recycling of other receptors, like the insulin receptor.…”

Section: Role Of Arc1 In Insulin Signaling In Gf Fliesmentioning

confidence: 99%

“…Accordingly, reduced Arc expression impairs memory formation and learning ability in rodents (Guzowski et al, 2000;Shandilya and Gautam, 2020), and defects in human Arc function have been linked to a variety of neurological and neurodevelopmental disorders, including Alzheimer's disease (Bi et al, 2018), autism spectrum disorders (Alhowikan, 2016), and schizophrenia (Fromer et al, 2014). Arc partially regulates synaptic plasticity by interacting with endocytic machinery to regulate synaptic surface presentation of AMPA-type glutamate receptors (Chowdhury et al, 2006;DaSilva et al, 2016;Wall and Corrêa, 2018). Both mammalian Arc and fly Arc1 encode retroviral group-specific antigen-like amino acid sequences, and are predicted to have independently derived from ancient Ty3/Gypsy retrotransposons (Ashley et al, 2018;Campillos et al, 2006;Cottee et al, 2019;Pastuzyn et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Arc1 and the microbiota together modulate growth and metabolic traits inDrosophila

Keith

Bishop

Fallacaro

et al. 2020

Preprint

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Perturbations to animal-associated microbial communities (the microbiota) have deleterious effects on various aspects of host fitness, including dysregulated energy metabolism. However, the molecular processes underlying these microbial impacts on the host are poorly understood. In this study, we identify a novel connection between the microbiota and the neuronal factor Arc1 that affects metabolism and development in Drosophila. We find that Arc1 exhibits tissue-specific microbiota-dependent expression changes, and that flies bearing a null mutation of Arc1 complete larval development at a dramatically slowed rate compared to wild-type animals. In contrast, monoassociation with a single Acetobacter sp. isolate was sufficient to enable Arc1 mutants to develop at a wild-type rate. These developmental phenotypes are highly sensitive to composition of the larval diet, suggesting the growth rate defects of GF flies lacking Arc1 reflect metabolic dysregulation. Additionally, we show that pre-conditioning the larval diet with Acetobacter sp. partially accelerates Arc1 mutant development, but live bacteria are required for the full growth rate promoting effect. Finally, GF Arc1 mutants display multiple traits consistent with reduced insulin signaling activity that are reverted by association with Acetobacter sp., suggesting a potential mechanism underlying the microbe-dependent developmental phenotypes. Our results reveal a novel role for Arc1 in modulating insulin signaling, metabolic homeostasis, and growth rate that is specific to the host’s microbial and nutritional environment.SUMMARYDrosophila Arc1 exhibits microbiota-dependent, tissue-specific differential expression, mitigates the impacts of germ-free rearing on insulin signaling and growth rate, but is dispensable for metabolic homeostasis in Acetobacter-colonized flies.

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The mechanistic link between Arc/Arg3.1 expression and AMPA receptor endocytosis

Cited by 36 publications

References 87 publications

Cross-modal reaction of auditory and visual cortices after long-term bilateral hearing deprivation in the rat

Cross-modal reaction of auditory and visual cortices after long-term bilateral hearing deprivation in the rat

A High-content Assay for Monitoring AMPA Receptor Trafficking

Arc1 and the microbiota together modulate growth and metabolic traits inDrosophila

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