CAST: Functional scaffold for the integrity of the presynaptic active zone

Cytomatrix at the active zone (CAZ)-associated structural protein (CAST) was first purified from the synaptic junction fraction of biochemically isolated central nervous system, and initially implicated as a critical component of the active zone. Subsequent biochemical analysis of CAST has shown that CAST potentially form a large molecular complex with other CAZ proteins including RIMs, Munc13s, Bassoon, and Piccolo/Aczonin in nerve terminals. Furthermore, recent genetic approaches using animal models such as C. elegans, Drosophila and mice have revealed that CAST has important functional and organizational roles in the assembly and maintenance of the presynaptic active zone. In this update article, I would like to summarize recent findings that place CAST as a functional scaffold regulating voltage-dependent Ca2+ channels and maintaining the integrity of the presynaptic active zone.