The presynaptic particle web: Ultrastructure, composition, dissolution, and reconstitution

We report the purification of a presynaptic "particle web" consisting of si milar to 50 nm pyramidally shaped particles interconnected by similar to 10 0 nm spaced fibrils. This is the "presynaptic grid" described in early EM s tudies. It is completely soluble above pH 8, but reconstitutes after dialys is against pH 6. Interestingly, reconstituted particles orient and bind PSD s asymmetrically. Mass spectrometry of purified web components reveals majo r proteins involved in the exocytosis of synaptic vesicles and in membrane retrieval. Our data support the idea that the CNS synaptic junction is orga nized by transmembrane adhesion molecules interlinked in the synaptic cleft , connected via their intracytoplasmic domains to the presynaptic web on on e side and to the postsynaptic density on the other. The CNS synaptic junct ion may therefore be conceptualized as a complicated macromolecular scaffol d that isostatically bridges two closely aligned plasma membranes.