At present, our interest is to determine the physiological role of tubulin's post-translational tyrosination/detyrosination. As strategy, we are trying to modify the terminal-COOH of alpha tubulin chain in different ways, hoping to detect an alteration in the cell functioning. Knowledge of the altered function could help us to conceive an idea regarding the role of this post-translational modification, and to perform the appropriate experiments to confront the stated hypothesis. We are trying to modify the carboxy-terminus by two methods: 1) substitution of the tyrosine at the carboxy-terminus with tyrosine analogues; up to now we have found various analogues with the capacity of incorporating into tubulin in place of tyrosine. 2) transfection of cells with the alpha-tubulin gene, with a previous modification of the codon corresponding to the tyrosine at the carboxy-terminus for another amino acid, or modifying the length of the carboxy-terminus with a few amino acids of difference. Besides the cellular morphology, the proliferation rate, the cellular viability, and the architecture of the cytoskeleton network, we are planning to examine the effect on more subtle functions of the modifications introduced in tubulin such as microtubule dynamics, intracellular transport, enzymes association, the motors and MAPs, interaction with other elements of the cytoskeleton, the adhesion to the substrate, the association with compounds implied in cellular signaling, cell-cell interaction, etc.