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Accueil > Bibliographie > Calcium-dependent regulation of SNARE-mediated membrane fusion by (...)

Calcium-dependent regulation of SNARE-mediated membrane (...)

J Biol Chem. 2010 Jul ;285(31):23665-75
Calcium-dependent regulation of SNARE-mediated membrane fusion by calmodulin.
Di Giovanni J, Iborra C, Maulet Y, Leveque C, El Far O, Seagar M.

Neuroexocytosis requires SNARE proteins, which assemble into trans complexes at the synaptic vesicle / plasma membrane interface and mediate bilayer fusion. Ca2+-sensitivity is thought to be conferred by synaptotagmin, although the ubiquitous Ca2+-effector calmodulin has also been implicated in SNARE-dependent membrane fusion. To examine the molecular mechanisms involved, we examined the direct action of calmodulin and synaptotagmin in vitro, using fluorescence resonance energy transfer to assay lipid-mixing between t- and v-SNARE liposomes. Ca2+/calmodulin inhibited SNARE assembly and membrane fusion by binding to two distinct motifs located in the membrane-proximal regions of VAMP2 (KD = 500nM) and syntaxin 1 (KD = 2 microM). In contrast, fusion was increased by full-length synaptotagmin 1 anchored in v-SNARE liposomes. When synaptotagmin and calmodulin were combined, synaptotagmin overcame the inhibitory effects of calmodulin. Furthermore synaptotagmin displaced calmodulin binding to t-SNAREs. These findings suggest that two distinct Ca2+ sensors act antagonistically in SNARE-mediated fusion.


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