The presynaptic cytomatrix of brain synapses

Synapses are principal sites for communication between neurons via chemical messengers called neurotransmitters. Neurotransmitters are released from p resynaptic nerve terminals at the active zone, a restricted area of the cel l membrane situated exactly opposite to the postsynaptic neurotransmitter r eception apparatus. At the active zone neurotransmitter-containing synaptic vesicles (SVs) dock, fuse, release their content and are recycled in a str ictly regulated manner. The cytoskeletal matrix at the active zone (CAZ) is thought to play an essential role in the organization of this SV cycle. Se veral multi-domain cytoskeleton-associated proteins, including RIM, Bassoon , Piccolo/Aczonin and Munc-13, have been identified, which are specifically localized at the active zone and thus are putative molecular components of the CAZ. This review will summarize our present knowledge about the struct ure and function of these CAZ-specific proteins. Moreover, we will review o ur present view of how the exocytotic and endocytic machineries at the site of neurotransmitter release are linked to and organized by the presynaptic cytoskeleton. Finally, we will summarize recent progress that has been mad e in understanding how active zones are assembled during nervous system dev elopment.