Structure Analysis of Synaptic Vesicles by Solution Small-Angle Scattering of X-Rays

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The release of neurotransmitters from neurons, in response to stimulation, forms the basis of communication in the nervous system. Neurotransmitters are stored in small membraneous organelles, synaptic vesicles (SVs), within the presynaptic terminal. These vesicles undergo an elaborate cycle of fusion with the plasma membrane (releasing neurotransmitter), followed by retrieval and reformation and transport back to the plasma membrane for further rounds of fusion [1].In recent years there has been enormous progress in our knowledge of the molecular composition and structure of synaptic vesicles [2]. However, we still lack a detailed view of the physical properties of this trafficking organelle as it proceeds through its life-cycle.Here we use small-angle x-ray scattering (SAXS) to determine the average radial density profile rho(r) and the size polydispersity of SVs [3]. We show that SAXS can be used to study the supra-molecular structure of an entire functional organelle under physiological conditions. The profile rho(r) of SVs including structural parameters of the protein layers, as well as the polydispersity function p(R), are derived with no free prefactors on an absolute scale. The measured SV structure on length scales between the constituent biomolecules and the SV size confirms the main aspects of recent numerical modeling [2], which was based on the crystal structures of the constituent proteins and stoichiometric knowledge from biochemical studies. In addition, we present first evidence of a laterally anisotropic structure, indicative of larger protein clusters.[1] T. Sudhof, Annu. Rev. Neurosci. 27 (2004) 509.[2] S. Takamori et al, Cell 127 (2006) 831.[3] S. Castorph et al, in preparation.