CAST and ELKS proteins: structural and functional determinants of the presynaptic active zone

Cytomatrix at the active zone-associated structural protein (CAST) was first purified from rat brain. It belongs to a protein family with the protein ELKS being its close relative. In nerve terminals, these proteins are specifically localized in the active zone (AZ). They have been shown to directly interact with other AZ proteins, including RIM1, Piccolo and Bassoon, and indirectly with Munc13-1 through RIM1, forming a large molecular complex at AZ. Moreover, the direct interaction of CAST with RIM1 and Bassoon appears to be involved in the release of neurotransmitters. However, it still remains elusive how CAST and ELKS regulate the assembly and function of AZ during synapse maturation. This review focuses on recent findings about the ELKS/CAST family revealed by biochemical strategies and genetic studies, and discusses the potential roles of this protein family in the function and organization of the presynaptic AZ.