Type 1 equilibrative nucleoside transporter regulates astrocyte‐specific glial fibrillary acidic protein expression in the striatum

Hinton, David J.; Lee, Moonnoh R.; Jang, Jin Sung; Choi, Doo Sup

doi:10.1002/brb3.283

Cited by 14 publications

(9 citation statements)

References 62 publications

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“…29 Consequently, we utilized the proteomic library obtained during a previous iTRAQ proteome investigation of the NAc as a reference to confirm our current label-free findings, which identified EAAT2, neurogranin (NRGN), and PKCγ and GFAP, as differentially altered in ENT1 −/− mice. 27,30 …”

Section: Discussionmentioning

confidence: 99%

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

et al. 2017

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The neural circuit of the dorsal hippocampus (dHip) and nucleus accumbens (NAc) contributes to cue-induced learning and addictive behaviors, as demonstrated by the escalation of ethanol-seeking behaviors observed following deletion of the adenosine equilibrative nucleoside transporter 1 (ENT1−/−) in mice. Here we perform quantitative LC–MS/ MS neuroproteomics in the dHip and NAc of ENT1−/− mice. Using Ingenuity Pathway Analysis, we identified proteins associated with increased long-term potentiation, ARP2/3-mediated actin cytoskeleton signaling and protein expression patterns suggesting deficits in glutamate degradation, GABAergic signaling, as well as significant changes in bioenergetics and energy homeostasis (oxidative phosphorylation, TCA cycle, and glycolysis). These pathways are consistent with previously reported behavioral and biochemical phenotypes that typify mice lacking ENT1. Moreover, we validated decreased expression of the SNARE complex protein VAMP1 (synaptobrevin-1) in the dHip as well as decreased expression of pro-dynorphin (PDYN), neuroendocrine convertase (PCSK1), and Leu-Enkephalin (dynorphin-A) in the NAc. Taken together, our proteomic approach provides novel pathways indicating that ENT1-regulated signaling is essential for neurotransmitter release and neuropeptide processing, both of which underlie learning and reward-seeking behaviors.

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Section: Discussionmentioning

confidence: 99%

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

et al. 2017

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“…Losses of GFAP resulted in an inability to traffic the glial GLT‐1 to the surface of the cell following PKA stimulation by dibutyryl‐cAMP (Hughes, Maguire, McMinn, Scholz, & Sutherland, ). In addition, GLT‐1 and AQP4 were downregulated in the striatum of mice lacking type 1 equilibrative nucleoside transporter that mainly reduced GFAP gene expression (Hinton, Lee, Jang, & Choi, ). These phenomena highlight that normal functions of GFAP are essential for the relocalization of astrocytic proteins.…”

Section: Gfap Functionsmentioning

confidence: 99%

Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes

Liu

et al. 2019

Glia

116

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Glial fibrillary acidic protein (GFAP), a type III intermediate filament, is a marker of mature astrocytes. The expression of GFAP gene is regulated by many transcription factors (TFs), mainly Janus kinase‐2/signal transducer and activator of transcription 3 cascade and nuclear factor κ‐light‐chain‐enhancer of activated B cell signaling. GFAP expression is also modulated by protein kinase and other signaling molecules that are elicited by neuronal activity and hormones. Abnormal expression of GFAP proteins occurs in neuroinflammation, neurodegeneration, brain edema‐eliciting diseases, traumatic brain injury, psychiatric disorders and others. GFAP, mainly in α‐isoform, is the major component of cytoskeleton and the scaffold of astrocytes, which is essential for the maintenance of astrocytic structure and shape. GFAP also has highly morphological plasticity because of its quick changes in assembling and polymerizing states in response to environmental challenges. This plasticity and its corresponding cellular morphological changes endow astrocytes the functions of physical barrier between adjacent neurons and stabilizer of extracellular environment. Moreover, GFAP colocalizes and even molecularly associates with many functional molecules. This feature allows GFAP to function as a platform for direct interactions between different molecules. Last, GFAP involves transportation and localization of other functional proteins and thus serves as a protein transport guide in astrocytes. This guiding role of GFAP involves an elastic retraction and extension cytoskeletal network that couples with GFAP reassembling, transporting, and membrane protein recycling machinery. This paper reviews our current understanding of the expression and functions of GFAP as well as their regulation.

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“…In the CNS, diminished ENT1, with regards to addictive disorders has been directly associated with increased vulnerability to both goal-directed behavior and excessive ethanol drinking ( Choi et al, 2004 ; Nam et al, 2011 , 2013 ). Furthermore, impaired ENT1 expression and thus adenosine homeostasis results in a reduction in glial fibrillary acidic protein (GFAP), excitatory amino acid transporter type 2 (EAAT2) and aquaporin type 4 (AQP4) expression, and alters astrocyte function ( Wu et al, 2010 , 2011 ; Lee et al, 2013 ; Hinton et al, 2014a ). Additionally, either low levels or pharmacological inhibition of ENT1 contribute to cardioprotection due to elevated adenosine circulating levels ( Rose et al, 2010 ; Ramadan et al, 2014 ).…”

Section: Nts Beyond Transportmentioning

confidence: 99%

Emerging Roles of Nucleoside Transporters

2018

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Since human Nucleoside Transporters (hNTs) were identified by their activity as transport systems, extensive work has been done to fully characterize them at the molecular and physiological level. Many efforts have been addressed to the identification of their selectivity for natural substrates and nucleoside analogs used to treat several diseases. hNTs belong to two different gene families, SLC28 and SLC29, encoding human Concentrative Nucleoside Transporters (hCNTs) and human Equilibrative Nucleoside Transporters (hENTs), respectively. hCNTs and hENTs are integral membrane proteins, albeit structurally unrelated. Both families share common features as substrate selectivity and often tissue localization. This apparent biological redundancy may anticipate some different roles for hCNTs and hENTs in cell physiology. Thus, hENTs may have a major role in maintaining nucleoside homeostasis, whereas hCNTs could contribute to nucleoside sensing and signal transduction. In this sense, the ascription of hCNT1 to a transceptor reinforces this hypothesis. Moreover, some evidences could suggest a putative role of hCNT2 and hCNT3 as transceptors. The interacting proteins identified for hCNT2 suggest a link to energy metabolism. Moreover, the ability of hCNT2 and hCNT3 to transport adenosine links both proteins to purinergic signaling. On the other hand, the broad selectivity transporters hENTs have a crucial role in salvage pathways and purinergic signaling by means of nucleoside pools regulation. In particular, the two new hENT2 isoforms recently described together with hENT2 seem to be key elements controlling nucleoside and nucleotide pools for DNA synthesis. This review focuses on all these NTs functions beyond their mere translocation ability.

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Type 1 equilibrative nucleoside transporter regulates astrocyte‐specific glial fibrillary acidic protein expression in the striatum

Cited by 14 publications

References 62 publications

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter

Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes

Emerging Roles of Nucleoside Transporters

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