Evidence for the involvement of Tiam1 in axon formation

In cultured neurons, axon formation is preceded by the appearance in one of the multiple neurites of a large growth cone containing a labile actin net work and abundant dynamic microtubules. The invasion-inducing T-lymphoma an d metastasis 1 (Tiam1) protein that functions as a guanosine nucleotide exc hange factor for Rac1 localizes to this neurite and its growth cone, where it associates with microtubules. Neurons overexpressing Tiam1 extend severa l axon-like neurites, whereas suppression of Tiam1 prevents axon formation, with most of the cells failing to undergo changes in growth cone size and in cytoskeletal organization typical of prospective axons. Cytochalasin D r everts this effect leading to multiple axon formation and penetration of mi crotubules within neuritic tips devoid of actin filaments. Taken together, these results suggest that by regulating growth cone actin organization and allowing microtubule invasion within selected growth cones, Tiam1 promotes axon formation and hence participates in neuronal polarization.