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RESEARCH ARTICLE |
1
Laboratorio di Biologia Cellulare, Istituto Superiore di
Sanità, Rome, Italy
2
Dipartimento di Biotechnologie Cellulari ed Ematologia,
Università La Sapienza, Rome, Italy
*
Author for correspondence (e-mail:
Gigliani{at}bce.med.uniroma1.it
)
Accepted May 1, 2001
To analyze the mechanism of Tat-mediated HIV pathogenicity, we produced a Drosophila melanogaster strain transgenic for HIV-tat gene and induced the expression of the protein during Drosophila development. By in vitro and in vivo experiments, we demonstrated that Tat specifically binds to tubulin via the MAP-binding domain of tubulin, and that this interaction delays the polymerization of tubulin and induces a premature stop to microtubule-dependent cytoplasmic streaming. The delay in the polymerization of microtubules, the tracks for the transport of the axes determinants, alters the positioning of the dorso-ventral axis as shown by the mislocalization of Gurken and Kinesin in oocyte of Drosophila after Tat induction. These results validate the use of Drosophila as a tool to study the molecular mechanism of viral gene products and suggest that Tat-tubulin interaction is responsible for neurodegenerative diseases associated with AIDS.
Key words: Tat-tubulin interaction, Microtubule polymerization, Tat, Cell polarization
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