BASSOON, A NOVEL ZINC-FINGER CAG GLUTAMINE-REPEAT PROTEIN SELECTIVELYLOCALIZED AT THE ACTIVE ZONE OF PRESYNAPTIC NERVE-TERMINALS/

The molecular architecture of the cytomatrix of presynaptic nerve term inals is poorly understood. Here we show that Bassoon, a novel protein of >400,000 M-r, is a new component of the presynaptic cytoskeleton. The murine bassoon gene maps to chromosome 9F. A comparison with the c orresponding rat cDNA identified 10 exons within its protein-coding re gion. The Bassoon protein is predicted to contain two double-zinc fing ers, several coiled-coil domains, and a stretch of polyglutamines (24 and 11 residues in rat and mouse, respectively), In some human protein s, e.g., Huntingtin, abnormal amplification of such polyglutamine regi ons causes late-onset neurodegeneration. Bassoon is highly enriched in synaptic protein preparations. In cultured hippocampal neurons, Basso on colocalizes with the synaptic vesicle protein synaptophysin and Pic colo, a presynaptic cytomatrix component. At the ultrastructural level , Bassoon is detected in axon terminals of hippocampal neurons where i t is highly concentrated in the vicinity of the active zone. Immunogol d labeling of synaptosomes revealed that Bassoon is associated with ma terial interspersed between clear synaptic vesicles, and biochemical s tudies suggest a tight association with cytoskeletal structures. These data indicate that Bassoon is a strong candidate to be involved in cy tomatrix organization at the site of neurotransmitter release.