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The Journal of Neuroscience, April 1, 2001, 21(7):2361-2372

Evidence for the Involvement of Tiam1 in Axon Formation

Patricia Kunda¹, Gabriela Paglini¹, Santiago Quiroga², Kenneth Kosik³, and Alfredo Cáceres¹

¹ Instituto Mercedes y Martín Ferreyra (INIMEC-CONICET), 5000 Cordoba, Argentina, ² Departamento Química Bíologica (CIQUIBIC-CONICET), Universidad Nacional Córdoba, 5000 Córdoba, Argentina, and ³ Department of Neurology (Neuroscience), Harvard Medical School and Center for Neurological Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115

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 network and abundant dynamic microtubules. The invasion-inducing T-lymphoma and metastasis 1 (Tiam1) protein that functions as a guanosine nucleotide exchange factor for Rac1 localizes to this neurite and its growth cone, where it associates with microtubules. Neurons overexpressing Tiam1 extend several 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 reverts this effect leading to multiple axon formation and penetration of microtubules 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.

Key words: Tiam1; microtubules; microfilaments; axons; growth cones; polarity

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Copyright © 2001 Society for Neuroscience  0270-6474/01/2172361-12$05.00/0

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