Trio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts

The well-studied members of the Trio family of proteins are Trio and kalirin in vertebrates, UNC-73 in Caenorhabditis elegans and Trio in Drosophila. Trio proteins are key regulators of cell morphogenesis and migration, tissue organization, and secretion and protein trafficking in many biological contexts. Recent discoveries have linked Trio and kalirin to human disease, including neurological disorders and cancer. The genes for Trio family proteins encode a series of large multidomain proteins with up to three catalytic activities and multiple scaffolding and protein–protein interaction domains. As such, Trio family proteins engage a wide array of cell surface receptors, substrates and interaction partners to coordinate changes in cytoskeletal regulatory and protein trafficking pathways. We provide a comprehensive review of the specific mechanisms by which Trio family proteins carry out their functions in cells, highlight the biological and cellular contexts in which they occur, and relate how alterations in these functions contribute to human disease.