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N°29 I quarterly I Ap ril 2013 Live from the Labs | 9 w Neurobiology To transport the vesicles that contain factors such as neurotransmitters along their axons, neurons rely on glycolysis. Unexpected Energy Use in Neurons BY Clémentine Wallace Fast axonal transport (FAT) is the means by which neurotransmitters and trophic factors—encapsulated inside vesicles that need a constant supply of energy to be propelled—are carried along neuronal extensions. “Yet there is a paradox,” says Frederic Saudou from the Curie Institute.1 “While vesicles require this permanent energy input to fuel their molecular motors, mitochondria, the main energy suppliers for cellular functions, are not evenly distributed within neurons. In some regions, they are even entirely absent.” Saudou and his team recently solved this enigma by demonstrating that FAT does not rely on mitochondrial energy.2 When researchers pharmacologically inhibited mitochondrial production in rat neuron cultures, vesicle motility remained unaffected. “We therefore turned our attention to the most elementary form of energy production in the cell—glycolysis— which relies on the first steps of glucose transformation,” explains Saudou. “Glucose is indeed the main source of energy for the brain.” The team inhibited the key enzyme involved in glycolysis, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and observed that transport was indeed significantly reduced. Further experiments using immunofluorescence and electron microscopy showed that each vesicle propelled by FAT carries its own GAPDH enzyme at its surface. “After silencing all GAPDH expression in neurons, we observed that re- attaching active GAPDH onto vesicles was sufficient to restore their mobility,” says Saudou. “So we looked at the physiological mechanisms by which GAPDH is attached to vesicles.” The team had previously shown that huntingtin—the protein that causes Huntington’s disease when mutated— was essential for vesicular transport. Could it also be involved in the attachment of GAPDH to vesicles? Using genetic engineering and immunofluorescence in vitro, the team showed that mutating huntingtin indeed caused GAPDH to detach from vesicles. “This led to a strong reduction in their motility, which again could be offset by artificially re attaching active GAPDH onto the vesicles,” says Saudou. By revealing the crucial role played by huntingtin in FAT, this study could improve understanding of the development of Huntington’s disease— a pathology characterized by neuronal degeneration. The researchers are exploring this new avenue. 01. Institut Curie (CNRS / Inserm). 02. D. Zala et al., “Vesicular glycolysis provides on-board energy for fast axonal transport,” Cell, 2013. 152(3): 479-91. Contact information: Institut Curie, Orsay. Frédéric Saudou > frederic.saudou@curie.fr BY Valerie Herczeg furnishings, so as to shed light on the deity worshipped in the sanctuary. While the statue’s back pillar bears no epigraph, the researchers believe it to be that of a local dignitary from Armant or even Thebes, whose name and position will forever remain a mystery. “Not only is the sculpture exceptional in terms of style and craftsmanship, but its dating would provide valuable information on the site’s history,” says Thiers. “We can only hope to find the head of this anonymous figure.” And for this silent witness of the past to reveal some of his secrets. 01. C entre Franco-Egyptien pour l’étude du temple de Karnak (CFEET K) (CNRS / Egypt’s Ministry of State for Antiquities); Archéologie des Sociétés Méditerranéennes (CNRS / Université Montpellier-III / INRA P / Ministère de la culture et de la communication). Contact information: CFEET K, Cairo. Christophe Thiers > christophe.thiers@univ-montp3.fr qGA PDH (green), present all over neurons, allow for the transport of vesicles (red) along the axons. 10 μm Orsay © D. Zala


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