The scaffold protein, Homer1b/c, regulates axon pathfinding in the centralnervous system in vivo

Homer proteins are a family of multidomain cytosolic proteins that have bee n postulated to serve as scaffold proteins that affect responses to extrace llular signals by regulating protein-protein interactions. We tested whethe r Homer proteins are involved in axon pathfinding in vivo, by expressing bo th wild-type and mutant isoforms of Homer in Xenopus optic tectal neurons. Time-lapse imaging demonstrated that interfering with the ability of endoge nous Homer to form protein-protein interactions resulted in axon pathfindin g errors at stereotypical choice points. These data demonstrate a function for scaffold proteins such as Homer in axon guidance. Homer may facilitate signal transduction from cell-surface receptors to intracellular proteins t hat govern the establishment of axon trajectories.