Arc protein: a flexible hub for synaptic plasticity and cognition

Nikolaienko, Oleksii; Patil, Sudarshan; Eriksen, Maria Steene; Bramham, Clive R.

doi:10.1016/j.semcdb.2017.09.006

Cited by 153 publications

(121 citation statements)

References 95 publications

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“…Finally, Arc regulated genes associated with altered cognitive function, a characteristic of AD (Mmp13, Pdyn, Tac1, Bdnf, Nr4a2, Penk, Pltp and Ccl2). To date, presenilin 1 (Psen1) and glycogen synthase kinase 3 beta (Gsk3b) are the only AD mediators which have been reported to physically associate and interact with Arc [78][79][80] . Arc also interacts with endophilin 2/3 and dynamin and recruits them to early/recycling endosomes to traffic APP and beta secretase 1 (BACE1), crucial determinants of AD progression 80 .…”

Section: Arc Knockdown Changes the Expression Of Genes Involved In Thmentioning

confidence: 99%

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Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease

Leung

Gwq

VanDongen

2019

Preprint

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The immediate-early gene Arc is a master regulator of synaptic function and a critical determinant of memory consolidation. Arc protein is localized to excitatory synapses, where it controls AMPA receptor endocytosis, and to the nucleus, where it associates with Tip60, a subunit of a chromatin modifying complex. Here we show that Arc interacts with dynamic chromatin loops and associates with histone markers for active enhancers and transcription in cultured hippocampal neurons. When Arc induction by pharmacological network activation was prevented using a short hairpin RNA, the expression profile was altered for over 1900 genes. Many gene families were affected by the absence of Arc, most notably those associated with synaptic function, neuronal plasticity, intrinsic excitability (channels, receptors, transporters), and signaling pathways (transcription factors/regulators). Interestingly, about 100 genes whose activitydependent expression level depends on Arc are associated with the pathophysiology of Alzheimer's disease, suggesting a critical role for Arc in the development of neurodegenerative disorders. When endogenous Arc expression was induced in a non-neuronal cell line (HEK293T), the transcription of many neuronal genes was increased, suggesting Arc can control expression in the absence of activated signaling pathways. Taken together, these data establish Arc as a master regulator of neuronal activity-dependent gene expression and a significant factor underlying the pathophysiology Alzheimer's disease.

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Section: Arc Knockdown Changes the Expression Of Genes Involved In Thmentioning

confidence: 99%

“…6). The domain structure of Arc protein appears to rule out that it can function as a transcription factor 78 . This raises the question: how does Arc regulate transcription?…”

Section: How Does Arc Regulate Transcription?mentioning

confidence: 99%

Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease

Leung

Gwq

VanDongen

2019

Preprint

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“…Interestingly, the REM-dependent pruning and strengthening of newly formed spines after learning was dependent on the activation of the NMDAr (Fig. 4d), increased calcium signaling specifically in the dendrites related to the mnemonic trace, and CaMKII activation, which in turn, can interact with Arc [210] (for a review see [211]).…”

Section: Selective Pruning and Maintenance Of Synapses By Post-trainimentioning

confidence: 99%

Memory corticalization triggered by REM sleep: mechanisms of cellular and systems consolidation

Almeida-Filho

Queiroz

Ribeiro

2018

Cell. Mol. Life Sci.

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Once viewed as a passive physiological state, sleep is a heterogeneous and complex sequence of brain states with essential effects on synaptic plasticity and neuronal functioning. Rapid-eye-movement (REM) sleep has been shown to promote calcium-dependent plasticity in principal neurons of the cerebral cortex, both during memory consolidation in adults and during post-natal development. This article reviews the plasticity mechanisms triggered by REM sleep, with a focus on the emerging role of kinases and immediate-early genes for the progressive corticalization of hippocampus-dependent memories. The body of evidence suggests that memory corticalization triggered by REM sleep is a systemic phenomenon with cellular and molecular causes.

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“…In LTP consolidation, SUMOylated Arc forms a complex with Drebrin as well, a major regulator of cytoskeletal dynamics in dendritic spines [16]. Thus, Arc protein interacts with distinct protein partners to participate in the regulation of multiple forms of synaptic plasticity [17]. Interestingly, we previously demonstrated that HSV-1 acute infection increases Arc mRNA and protein expression in different neuronal cell lines, and the up-regulation is dependent of an active viral replicative cycle [18].…”

Section: Introductionmentioning

confidence: 99%

Herpes Simplex Virus type 1 neuronal infection triggers disassembly of key structural components of dendritic spines

Acuña‐Hinrichsen

Covarrubias‐Pinto

Ishizuka

et al. 2020

Preprint

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Herpes simplex virus type 1 (HSV-1) is a widespread neurotropic virus. The primary infection in facial epithelium leads to retrograde axonal transport to the central nervous system (CNS) where it establishes latency. Under stressful conditions, the virus reactivates, and new progeny is transported anterogradely to the primary site of infection. In late stages of neuronal infection, axonal damage is known to occur. However, the impact of HSV-1 infection on morphology and functional integrity at earlier stages of infection in neuronal dendrites is unknown. Previously, we demonstrated that acute HSV-1 infection in neuronal cell lines selectively enhances the expression of Arc protein -a major regulator of long-term synaptic plasticity and memory consolidation, known for being a protein-interaction hub in the postsynaptic dendritic compartment. Thus, HSV-1 induced Arc may alter the functionality of the infected neurons having an impact on dendritic spine dynamics. In this study we demonstrated that HSV-1 infection causes structural disassembly and functional deregulation in cultured cortical neurons, through protein homeostasis alteration with intracellular accumulation of Arc, and decreased expression of spine scaffolding-like proteins such as PSD-95, Drebrin and CaMKIIβ. Our findings reveal progressive deleterious effects of HSV-1 infection on excitatory neuronal synapse function and dendritic morphology, supporting the thesis of the infectious origin of neurodegenerative processes.

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Arc protein: a flexible hub for synaptic plasticity and cognition

Cited by 153 publications

References 95 publications

Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease

Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease

Memory corticalization triggered by REM sleep: mechanisms of cellular and systems consolidation

Herpes Simplex Virus type 1 neuronal infection triggers disassembly of key structural components of dendritic spines

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