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Des microtubules détyrosinés : quelles conséquences pour la cellule?

Abstract : Microtubules (MT) are dynamic structures involved in different essential processes of cell architecture.
Particularly, MT plus ends (+ends) can accumulate specific proteins controlling MT dynamics and MT interaction with the cell cortex. These interactions are implicated in the correct positionning of the mitotic spindle. Description of the mechanisms of protein association with MT +ends is important to understand MT functions. C-terminal tyrosine of α-tubulin is crucial for the interaction of CAP-Gly domain containing proteins.
Indeed, CLIP-170 and its S. cerevisiae homolog Bik1p bind less efficiently to MT deleted for the C-terminal tyrosine (Glu MT).
In this work, we studied the consequences of low Bik1p association with Glu MT +ends.
Current models propose that Bik1p is targeted towards MT +ends by the kinesin Kip2p. Dynein (Dyn1p) is,
then, recruited by Bik1p at MT +ends and offloaded at the cortex. Here, we show that, in yeast cells expressing only
detyrosinated tubulin (tub1-Glu strain), Kip2p and Dyn1p are correctly associated with MT +ends, despite the
decreased Bik1p binding. We propose that, in wild type cells, the Kip2p/Bik1p complex transports Dyn1p along MT towards MT +ends. Then, Kip2p, Bik1p and Dyn1p track MT +ends independently.
Moreover, we show that constituvely active forms of the small G protein Rho1p favour Bik1p binding to MT +ends. These data will be important to understand the role of Rho GTPases in the regulation of MT, for instance during migration of mammalian cells.
Finally, we systematically searched for mutations that are lethal in combination with the tub1-Glu mutation
(synthetic lethality). This screen identified components important in the formation of cell membrane and cell wall.
These genes could be involved, at the cortex, in the establishment of microtubule-cortex interactions, and could show the importance of the α-tubulin C-terminal tyrosine in this function.
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https://tel.archives-ouvertes.fr/tel-00149555
Contributor : Fabrice Caudron <>
Submitted on : Saturday, May 26, 2007 - 6:05:30 PM
Last modification on : Friday, November 6, 2020 - 4:11:21 AM
Long-term archiving on: : Thursday, April 8, 2010 - 5:58:26 PM

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  • HAL Id : tel-00149555, version 1

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Fabrice Caudron. Des microtubules détyrosinés : quelles conséquences pour la cellule?. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2007. Français. ⟨tel-00149555⟩

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