Fig. 1. The Trio family. Members identified in vertebrates (Trio and Kalirin), C. elegans (UNC-73) and Drosophila share a series of N-terminal spectrin-like repeats, two GEF domains consisting of a DH domain coupled to a pleckstrin homology (PH) domain, and an SH3 domain located between the two GEF domains. The C-terminal of the molecule differs in all members identified thus far; human Trio encodes a second SH3 domain, an Ig-like domain and a serine/threonine kinase (STK) domain, kalirin encodes two Ig-like repeats and an STK domain, UNC-73 possesses an Ig-like repeat and a fibronectin-like repeat (FNIII), and Drosophila Trio terminates immediately following the C-terminal PH domain. In addition to the molecules depicted, several alternatively spliced variants have been described for kalirin and UNC-73.