The active zone defines the area of the presynaptic plasma membrane where synaptic vesicles (SV) dock, mature, and fuse with the cell membrane in a regulated manner. The active zone is defined by an electron-dense cytomatrix of specialized proteins, the cytomatrix assembled at the active zone (CAZ). Some of these proteins, e.g., RIMs, Munc13s, ERC/CASTs as well as Bassoon and Piccolo are exclusive components of the CAZ, and are thought to mediate specific functions, including the localization and regulation of the SV cycle. Recently, major progress has been achieved in studying the assembly of the active zone and the underlying cytoskeletal matrix, suggesting it is not assembled 'brick-by-brick' as originally assumed. Rather, mounting evidence suggests that active zone components are preassembled within the neuronal soma, presumably at a trans-Golgi compartment, and then transported on distinct precursor vesicles to primordial presynaptic sites where they fuse with the cell membrane. As Piccolo and Bassoon are unique marker proteins of these vesicles they are called Piccolo-Bassoon transport vesicles (PTVs). The present review summarizes evidence for this active zone precursor vesicle hypothesis, which predicts that presynaptic active zones are assembled in a more or less quantal manner.

tInstitute for Anatomy and Cell Biology, University of Heidelberg, Im Neuenheimer Feld 307, D-69120 Heidelberg, Germany; [email protected] 'Leibniz Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany; [email protected]

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