Suppression of nuclear oscillations in Saccharomyces cerevisiae expressing Glu tubulin
- A. C. Badin-Larçon*,†,
- C. Boscheron*,†,‡,
- J. M. Soleilhac*,
- M. Piel§,
- C. Mann¶,
- E. Denarier*,
- A. Fourest-Lieuvin*,
- L. Lafanechère*,
- M. Bornens§, and
- D. Job*
- *Laboratoire du Cytosquelette, Commissariat à l'Energie Atomique Grenoble, Département de Réponse et Dynamique Cellulaire, Institut National de la Santé et de la Recherche Médicale U366, 38054 Grenoble, France; §Institut Curie, Section Recherche, Unite Mixte Recherche 144 du Centre National de la Recherche Scientifique, 75248 Paris Cedex 05, France; and ¶Service de Biochimie et de Génétique Moléculaire, Commissariat à l'Energie Atomique Saclay, 91191 Gif-sur-Yvette, France
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Edited by J. Richard McIntosh, University of Colorado, Boulder, CO, and approved January 30, 2004 (received for review December 1, 2003)
Abstract
In most eukaryotic cells, the C-terminal amino acid of α-tubulin is aromatic (Tyr in mammals and Phe in Saccharomyces cerevisiae) and is preceded by two glutamate residues. In mammals, the C-terminal Tyr of α-tubulin is subject to cyclic removal from the peptide chain by a carboxypeptidase and readdition to the chain by a tubulin–Tyr ligase. There is evidence that tubulin–Tyr ligase suppression and the resulting accumulation of detyrosinated (Glu) tubulin favor tumor growth, both in animal models and in human cancers. However, the molecular basis for this apparent stimulatory effect of Glu tubulin accumulation on tumor progression is unknown. Here we have developed S. cerevisiae strains expressing only Glu tubulin and used them as a model to assess the consequences of Glu tubulin accumulation in cells. We find that Glu tubulin strains show defects in nuclear oscillations. These defects are linked to a markedly decreased association of the yeast ortholog of CLIP170, Bik1p, with microtubule plus-ends. These results indicate that the accumulation of Glu tubulin in cells affects microtubule tip complexes that are important for microtubule interactions with the cell cortex.
Footnotes
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↵ ‡ To whom correspondence should be addressed at: Laboratoire du Cytosquelette, CEA Grenoble DRDC INSERM U366, 17 Rue des Martyrs, 38054 Grenoble, France. E-mail: cecile.buscheron{at}cea.fr.
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↵ † A.C.B.-L. and C.B. contributed equally to this work.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviations: TTL, tubulin-Tyr ligase; TLP, TTL-like protein.
- Copyright © 2004, The National Academy of Sciences
