Synaptophysin I selectively specifies the exocytic pathway of Synaptobrevin2/VAMP2

Dario Bonanomi , Laura Rusconi , Chiara A Colombo , Fabio Benfenati , Flavia Valtorta (1)

1 Neuroscience

Biogenesis and recycling of synaptic vesicles are accompanied by sorting processes that preserve the molecular composition of the compartments involved. In this study we address the targeting of synaptobrevin2/vesicle associated membrane protein 2 (VAMP2), a critical component of the synaptic vesicle fusion machinery, in a heterotypic context where its sorting is not confounded by the presence of other neuron-specific molecules. Ectopically-expressed synaptophysin I interacts with VAMP2 and converts its default surface targeting to a prominent vesicular distribution, with no effects on the targeting of other membrane proteins. Protein-protein interaction is not sufficient for the control of VAMP2 sorting, which is mediated by the carboxy-terminal domain of synaptophysin I. Synaptophysin I directs the sorting of VAMP2 to vesicles prior to surface delivery, without influencing VAMP2 endocytosis. Consistently, dynamin and alpha-SNAP mutants which block trafficking at the plasma membrane do not occlude the effect of synaptophysin I on VAMP2 sorting. These results indicate that the sorting determinants of synaptic vesicle proteins can operate independently of a neuronal context and implicate the association of VAMP2 with synaptophysin I in the specification of the pathway of synaptic vesicle biogenesis.

Mots clés: Life Sciences

Dario Bonanomi, Laura Rusconi, Chiara A Colombo, Fabio Benfenati, Flavia Valtorta. Synaptophysin I selectively specifies the exocytic pathway of Synaptobrevin2/VAMP2. Biochemical Journal, 2007, 404 (3), pp.525-534. ⟨10.1042/BJ20061907⟩. ⟨hal-00478729⟩