Fachbereich Veterinärmedizin



    A Vital Role of Tubulin-Tyrosine-Ligase for Neuronal Organization (2005)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Erck, Christian
    Peris, Leticia
    Andrieux, Annie
    Meissirel, Claire
    Gruber, Achim D
    Vernet, Muriel
    Schweitzer, Annie
    Saoudi, Yasmina
    Pointu, Hervé
    Bosc, Christophe
    Salin, Paul A
    Job, Didier
    Wehland, Juergen
    Proceedings of the National Academy of Sciences of the United States of America; 102(22) — S. 7853–7858
    ISSN: 0027-8424
    Pubmed: 15899979
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
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    Abstract / Zusammenfassung

    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.