RGD Reference Report - GLUT4 Mobilization Supports Energetic Demands of Active Synapses. - Rat Genome Database

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GLUT4 Mobilization Supports Energetic Demands of Active Synapses.

Authors: Ashrafi, Ghazaleh  Wu, Zhuhao  Farrell, Ryan J  Ryan, Timothy A 
Citation: Ashrafi G, etal., Neuron. 2017 Feb 8;93(3):606-615.e3. doi: 10.1016/j.neuron.2016.12.020. Epub 2017 Jan 19.
RGD ID: 13702195
Pubmed: (View Article at PubMed) PMID:28111082
DOI: Full-text: DOI:10.1016/j.neuron.2016.12.020

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.

Gene Ontology Annotations    

Biological Process

Cellular Component
presynapse  (IDA,IMP)

Objects Annotated

Genes (Rattus norvegicus)
Slc2a4  (solute carrier family 2 member 4)

Additional Information