The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
GLUT4 Mobilization Supports Energetic Demands of Active Synapses
Open accessAbstract
SUMMARY The brain is highly sensitive to proper fuel availability as evidenced by the rapid decline in neuronal function during ischemic attacks and acute severe hypoglycemia. We previously showed that sustained presynaptic function requires activity-driven glycolysis. Here, we provide strong evidence that during action potential (AP) firing, nerve terminals rely on the glucose transporter Glut4 as a glycolytic regulatory system to meet the activity-driven increase in energy demands. Activity at synapses triggers insertion of Glut4 into the axonal plasma membrane driven by activation of the metabolic sensor AMP kinase. Furthermore, we show that genetic ablation of Glut4 leads to an arrest of synaptic vesicle recycling during sustained AP firing, similar to what is observed during acute glucose deprivation. The reliance on this biochemical regulatory system for “exercising” synapses is reminiscent of that occurring in exercising muscle to sustain cellular function, and identifies nerve terminals as critical sites of proper metabolic control.
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Cites
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Insulin-stimulated Phosphorylation of a Rab GTPase-activating Protein Regulates GLUT4 Translocation
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Activity-driven local ATP synthesis is required for synaptic function
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Self-citationCrystal structure of the human glucose transporter GLUT1
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Brain Glucose Metabolism: Integration of Energetics with Function
Dienel, G. A. (2019) · Physiological Reviews · doi:10.1152/physrev.00062.2017 · Cited by 865
Mitochondria at the neuronal presynapse in health and disease
Devine, M. J., & Kittler, J. T. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.170 · Cited by 615
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Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake
Díaz-García, C. M., Mongeon, R., Lahmann, C., Koveal, D., Zucker, H., & Yellen, G. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.021 · Cited by 466
“…we cannot exclude the possibility of ANLS activity at synaptic terminals, but recent results on metabolism at synaptic terminals of cultured rat neurons, and in C. elegans, support the idea that they too rely on direct neuronal metabolism of glucose (Ashrafi et al., 2017; Jang et al., 2016).”
Metadata
- Authors
- Ashrafi, G., Wu, Z., Farrell, R. J., & Ryan, T. A.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 93
- Issue
- 3
- Pages
- 606-615.e3
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2576833703
- Cited by
- 326
- References
- 41
- FWCI
- 12.68
- Type
- journal article
- Language
- en
- Open access
- bronze
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