Trio is a member of the Dbl homology (DH)1 family of guanine nucleotide exchange factors. These proteins activate the Rho GTPases and control actin cytoskeleton dynamics, cell adhesion, and gene transcription.
Trio contains two DH GEF domains in addition to a protein serine/threonine kinase and SH3-like domains, as well as several spectrin-like repeats. This multifunctional protein functions in a variety of biological processes, including axon guidance and neural migration.
TRIO controls vascular integrity
Endothelial cells have a critical role in maintaining the vascular barrier, which regulates blood flow and protects against inflammatory stimuli by regulating cell-cell interactions and adhesion molecules. Trio can function to promote the formation of adherens junctions and tight junctions, which are essential for vascular stability.
During axonogenesis, TRIO interacts with signaling proteins that control the direction of embryonic axons, including DRho1 and netrin-1. However, the interaction between TRIO and these components is complicated. Genetic studies of Drosophila retina indicate that TRIO may interact with a variety of proteins in the axon guidance pathway.
TRIO activates Rac1 during NC protrusions
Activating Rho and Rac is crucial for axon formation, but the precise mechanism by which TRIO mediates axon guidance depends on the specific guidance cues and cellular contexts of each axon. Using a Drosophila visual system as a model, we found that TRIO activates Rac1 during the formation of cranial NC protrusions by recruiting the Rac-like GTPases, DVL and Cad11.
We also found that loss of Trio significantly decreases embryonic Rac1 activity. Moreover, DVL expression rescues the phenotype of TRIO-/- embryos. These findings suggest that TRIO plays a major role in the development of the lateral cortex and may also have a functional role in the olfactory bulb, hippocampal formation and secondary myogenesis.