Aczonin, a 550-kD putative scaffolding protein of presynaptic active zones, shares homology regions with rim and bassoon and binds profilin

Neurotransmitter exocytosis is restricted to the active zone, a specialized area of the presynaptic plasma membrane. We report the identification and initial characterization of aczonin, a neuron-specific 550-kD protein conce ntrated at the presynaptic active zone and associated with a detergent-resi stant cytoskeletal subcellular fraction. Analysis of the amino acid sequenc es of chicken and mouse aczonin indicates an organization into multiple dom ains, including two pairs of Cys(4) zinc fingers, a polyproline tract, and a PDZ domain and two C2 domains near the COOH terminus. The second C2 domai n is subject to differential splicing. Aczonin binds profilin, an actin-bin ding protein implicated in actin cytoskeletal dynamics. Large parts of aczo nin, including the zinc finger, PDZ, and C2 domains, are homologous to Rim or to Bassoon, two other proteins concentrated in presynaptic active zones. We propose that aczonin is a scaffolding protein involved in the organizat ion of the molecular architecture of synaptic active zones and in the orche stration of neurotransmitter vesicle trafficking.