Tubulin tyrosination: a regulator of +TIPs and of microtubule stability
Microtubules (MTs) are key players in various cellular functions including mitosis,
morphogenesis and differentiation.
Tubulin, the basic block of MTs, is subject to specific post-translational modifications that
principally affect the C-terminus of the -subunit. One of these modifications known as the
tyrosination cycle involves the cyclic removal of the C-terminal tyrosine residue of the tubulin chain by a tubulin carboxypeptidase (TCP) and the addition of a tyrosine residue at the
same site by the tubulin-tyrosine-ligase (TTL). The tyrosination cycle is highly conserved
among eukaryotes and generates two pools of tubulin: Tyr-Tubulin and deTyr-Tubulin.
Initially we showed that TTL behaves as a potential tumor suppressor, being
frequently suppressed during tumor progression1. Using the yeast system Saccharomyces
cerevisiae we found that the Tyr-tubulin is required for the interaction of Bik1p (ortholog of
CLIP170) with microtubule + ends and thus for correct nuclear oscillations2. In mammalian
cells, we demonstrated that the C-terminal Tyrosine residue of alpha tubulin is crucial for
microtubules interaction with two classes of molecules: the + end binding proteins of the
CLIP family and the depolymerising motors of the Kin 13 family3. In the absence of TyrTubulin, the interaction between MTs and these two classes of effectors is impaired and
results both in 1/an abnormal cross talk between microtubules + ends and the cell cortex 2/an
abnormal MT stability. The cellular phenotypes associated with the removal of TTL include
anomalies in the control of spindle positioning which may promote tumour progression and in
aberrant neuronal morphogenesis4.
Complete comprehension of the cellular significance of tubulin tyrosination/detyrosination
cycle will rely on the identification and the characterisation of the tubulin carboxypeptidase
(TCP).
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4
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A. C. Badin-Larcon, C. Boscheron, J. M. Soleilhac et al., Proceedings of the National Academy of Sciences of the
United States of America 101 (15), 5577 (2004).
L. Peris, M. Wagenbach, L. Lafanechere et al., The Journal of cell biology 185 (7), 1159 (2009); L. Peris, M.
Thery, J. Faure et al., The Journal of cell biology 174 (6), 839 (2006).
C. Erck, L. Peris, A. Andrieux et al., Proceedings of the National Academy of Sciences of the United States of
America (2005).