NEW ROLES FOR FIBROUS MICROTUBULE ASSOCIATED PROTEINS DURING AXONAL DEVELOPMENT

SUNG CH; CHUANG JZ; YEH TY; BOLLATI F; CONDE C; CANAVOSIO F; CACERES A

Innsbruck

Congreso; 20th Biennial Meeting of the International Society for neurochemistry; 2005

Neurons are highly polarized cells that extend single long axons, and several much shorter but highly branched dendrites. Polarization occurs when one of the multiple neurites that arise from the cell body initiates a phase of rapid elongation, becoming the axon. Current views favor the view that one mechanism for the axon to differentiate from the other neurites relates with differences in cytoskeletal dynamics. Axon formation entails assembly and extension of microtubules within growth cones that contain abundant actin ?laments. It has been proposed that actin ?laments within axonal growth cones are more dynamic than those in other neurites, thereby allowing microtubule penetration and stabilization when neurons polarize. Unfortunately, the precise nature of the interaction between microtubules and micro?laments during neuronal polarization has remained largely unknown. We now show that the cytoplasmic dynein light chain Tctex-1 plays a key role in multiple steps of hippocampal neuron development, including initial neurite sprouting, axon speci?cation, and later dendritic elaboration. The neuritogenic effects elicited by Tctex-1 are independent from its cargo adaptor role for dynein motor transport. Finally, our data suggest that the selective high level of Tctex-1 at the growth cone of growing axons drives fast neurite extension by modulating actin dynamics. This effect involves recruitment and activation of Tiam1, a guanosine- nucleotide exchange for Rac, to the axonal growth cone.