Thu, 21 Aug 2008 15:33:40 BST CiteULike: lechristophe Wehland http://www.citeulike.org/user/lechristophe/author/Wehland CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/lechristophe/article/2234603 <i>J Cell Biol, Vol. 174, No. 6. (11 September 2006), pp. 839-849.</i><br /><br />Tubulin-tyrosine ligase (TTL), the enzyme that catalyzes the addition of a C-terminal tyrosine residue to alpha-tubulin in the tubulin tyrosination cycle, is involved in tumor progression and has a vital role in neuronal organization. We show that in mammalian fibroblasts, cytoplasmic linker protein (CLIP) 170 and other microtubule plus-end tracking proteins comprising a cytoskeleton-associated protein glycine-rich (CAP-Gly) microtubule binding domain such as CLIP-115 and p150 Glued, localize to the ends of tyrosinated microtubules but not to the ends of detyrosinated microtubules. In vitro, the head domains of CLIP-170 and of p150 Glued bind more efficiently to tyrosinated microtubules than to detyrosinated polymers. In TTL-null fibroblasts, tubulin detyrosination and CAP-Gly protein mislocalization correlate with defects in both spindle positioning during mitosis and cell morphology during interphase. These results indicate that tubulin tyrosination regulates microtubule interactions with CAP-Gly microtubule plus-end tracking proteins and provide explanations for the involvement of TTL in tumor progression and in neuronal organization. Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends. L Peris M Thery J Fauré Y Saoudi L Lafanechère JK Chilton P Gordon-Weeks N Galjart M Bornens L Wordeman J Wehland A Andrieux D Job doi:10.1083/jcb.200512058 J Cell Biol, Vol. 174, No. 6. (11 September 2006), pp. 839-849. 2008-01-15T10:57:11-00:00 2006 J Cell Biol 0021-9525 174 6 839 849 adhesion cell_culture centrosome cytosqueleton micropatterns microtubules tips http://www.citeulike.org/user/lechristophe/article/2191373 <i>Proc Natl Acad Sci U S A, Vol. 102, No. 22. (31 May 2005), pp. 7853-7858.</i><br /><br />Tubulin is subject to a special cycle of detyrosination/tyrosination in which the C-terminal tyrosine of alpha-tubulin is cyclically removed by a carboxypeptidase and readded by a tubulin-tyrosine-ligase (TTL). This tyrosination cycle is conserved in evolution, yet its physiological importance is unknown. Here, we find that TTL suppression in mice causes perinatal death. A minor pool of tyrosinated (Tyr-)tubulin persists in TTL null tissues, being present mainly in dividing TTL null cells where it originates from tubulin synthesis, but it is lacking in postmitotic TTL null cells such as neurons, which is apparently deleterious because early death in TTL null mice is, at least in part, accounted for by a disorganization of neuronal networks, including a disruption of the cortico-thalamic loop. Correlatively, cultured TTL null neurons display morphogenetic anomalies including an accelerated and erratic time course of neurite outgrowth and a premature axonal differentiation. These anomalies may involve a mislocalization of CLIP170, which we find lacking in neurite extensions and growth cones of TTL null neurons. Our results demonstrate a vital role of TTL for neuronal organization and suggest a requirement of Tyr-tubulin for proper control of neurite extensions. A vital role of tubulin-tyrosine-ligase for neuronal organization. C Erck L Peris A Andrieux C Meissirel AD Gruber M Vernet A Schweitzer Y Saoudi H Pointu C Bosc PA Salin D Job J Wehland doi:10.1073/pnas.0409626102 Proc Natl Acad Sci U S A, Vol. 102, No. 22. (31 May 2005), pp. 7853-7858. 2008-01-03T13:05:22-00:00 2005 Proc Natl Acad Sci U S A 0027-8424 102 22 7853 7858 cytosqueleton microtubules neurites_growth neurons tips transgenic