Piccolo, the pre-synaptic protein known for its involvement in the assembly of the active zone, exists in two variants, which properties are under investigation. A new structural study (J. Garcia et al. A conformational switch in the Piccolo C2A domain regulated by alternative splicing. Nature Struct. Mol. Biol. 11, 45-53, 2004) reported that C2A domain of Piccolo undergoes alternative splicing, which yields isoforms that might have different roles.

A stretch of nine amino acids in the C2A domain of Piccolo makes a structural difference with synaptotagmin: this segment is alternatively spliced resulting either in a short version of the protein or in a longer one. Splicing could constitute a mechanism for the regulation of C2 domains, which are present in a large number of proteins. Of course, to study the functional implications related to the existence of these two isoforms, it will be necessary to indagate their effects on the synaptic vesicle fusion. 


BM&L-February 2004