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Accueil > Agenda > Les séminaires Jean Roche > Local energy produced by glycolysis : on-board ATP fueling of intracellular (...)

Local energy produced by glycolysis : on-board ATP (...)

Mercredi 17 juin 2015 - 11 heures.

Docteur Diana ZALA ESPCI, Paris.

Local Energy produced by Glycolysis : On-board ATP fueling of intracellular trafficking.

Invité par Christophe LETERRIER – CRN2M UMR7286 - tél : 04 91 69 89 30.

Résumé :

Fast axonal transport (FAT) requires consistent energy over long distances to fuel the molecular motors that transport vesicles. We demonstrate that glycolysis provides ATP for the FAT of vesicles. Although inhibiting ATP production from mitochondria did not affect vesicles motility, pharmacological or genetic inhibition of the glycolytic enzyme GAPDH reduced transport in cultured neurons and in Drosophila larvae. GAPDH localizes on vesicles via a huntingtin-dependent mechanism and is transported on fast-moving vesicles within axons. Purified motile vesicles showed GAPDH enzymatic activity and produced ATP. Finally, we show that vesicular GAPDH is necessary and sufficient to provide on- board energy for fast vesicular transport. Although detaching GAPDH from vesicles reduced transport, targeting GAPDH to vesicles was sufficient to promote FAT in GAPDH deficient neurons. This specifically localized glycolytic machinery may supply constant energy, independent of mitochondria, for the processive movement of vesicles over long distances in axons.

Bibliographie :

Zala D, Hinckelmann MV, Yu H, Lyra da Cunha MM, Liot G, Cordelières FP, Marco S, Saudou F. Vesicular glycolysis provides on-board energy for fast axonal transport. Cell. 2013 Jan 31 ;152(3):479-91.

Zala D, Hinckelmann MV, Saudou F. Huntingtin’s function in axonal transport is conserved in Drosophila melanogaster. PLoS One. 2013 ;8(3):e60162.

Hinckelmann MV, Zala D, Saudou F. Releasing the brake : restoring fast axonal transport in neurodegenerative disorders. Trends Cell Biol. 2013 Dec ;23(12):634-43.

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