Chromophore-Assisted Light Inactivation of the V-ATPase V0c Subunit Inhibits Neurotransmitter Release Downstream of Synaptic Vesicle Acidification

authors

• Rama Sylvain
• Boumedine-Guignon Norah
• Sangiardi Marion
• Youssouf Fahamoe
• Maulet Yves
• Lévêque Christian
• Belghazi Maya
• Seagar Michael
• Debanne Dominique
• El Far Oussama

keywords

• Neurotransmission
• Neurons
• GeneGun Keywords V-ATPase
• V-ATPase
• Chromophore-assisted light inactivation CALI
• Hippocampal organotypic slice culture
• GeneGun

abstract

Synaptic vesicle proton V-ATPase is an essential component in synaptic vesicle function. Active acidification of synaptic vesicles, triggered by the V-ATPase, is necessary for neurotransmitter storage. Independently from its proton transport activity, an additional important function of the membrane-embedded sector of the V-ATPase has been uncovered over recent years. Subunits a and c of the membrane sector of this multi-molecular complex have been shown to interact with SNARE proteins and to be involved in modulating neurotransmitter release. The c-subunit interacts with the v-SNARE VAMP2 and facilitates neurotransmission. In this study, we used chromophore-assisted light inactivation and monitored the consequences on neuro-transmission on line in CA3 pyramidal neurons. We show that V-ATPase c-subunit V0c is a key element in modulating neurotransmission and that its specific inactivation rapidly inhibited neurotransmission.

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