Synapsin shields a lipid monolayer from interactions with vesicles and associated structural rearrangements.

Synapsins are the proteins responsible for recruiting synaptic vesicles into the synaptic vesicle cluster. As one of the most abundant synaptic proteins, synapsins are well known to directly interact with the synaptic vesicles, but they can also interact with planar membranes, notably the synaptic membrane, at least indirectly by tethering vesicles to the active zone. In order to contribute to a quantitative understanding of how interactions with synapsin affect the structure of a membrane already before neurotransmission, we use a minimal in vitro model of a lipid monolayer in contact with a subphase containing synapsin 1 and vesicles. We then probe the interface structure by x-ray reflectivity and grazing incidence diffraction at controlled surface pressure and monitor changes in lipid chain packing in the presence and absence of synapsin. In the absence of synapsin, injection of vesicles into the subphase below the film causes a pronounced reduction in lipid chain spacing, which further decreases by addition of calcium. This effect was muted when the film was first incubated with synapsin before injection of vesicles. We interpret this as a protective function of synapsin suppressing perturbation of the synaptic membrane, which could result in unwanted spontaneous fusion.