Proteomique CAPM

Accueil > Plates-formes PFRN > Proteomique CAPM > Calcium-dependent regulation of SNARE-mediated membrane fusion by (...)

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

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.

Voir en ligne : article 20519509



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