TTLL3 Is a Tubulin Glycine Ligase that Regulates the Assembly of Cilia

In most ciliated cell types, tubulin is modified by glycylation, a posttranslational modification of unknown function. We show that the TTLL3 proteins act as tubulin glycine ligases with chain-initiating activity. In Tetrahymena, deletion of TTLL3 shortened axonemes and increased their resistance to...

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Bibliographic Details
Published in:Developmental cell 2009-06, Vol.16 (6), p.867-876
Main Authors: Wloga, Dorota, Webster, Danielle M., Rogowski, Krzysztof, Bré, Marie-Hélène, Levilliers, Nicolette, Jerka-Dziadosz, Maria, Janke, Carsten, Dougan, Scott T., Gaertig, Jacek
Format: Article
Language:English
Subjects:
Animals
Axoneme - drug effects
Axoneme - enzymology
Axoneme - ultrastructure
Biological and medical sciences
Body Patterning - drug effects
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
CELLBIO
Cilia - drug effects
Cilia - enzymology
Cilia - ultrastructure
DEVBIO
Embryo, Nonmammalian - drug effects
Embryo, Nonmammalian - enzymology
Fundamental and applied biological sciences. Psychology
Gene Knockdown Techniques
Genes, Dominant
Glutamic Acid - metabolism
Glycine - metabolism
Ligases - metabolism
Molecular and cellular biology
Mutation - genetics
Oligonucleotides, Antisense - pharmacology
Peptide Synthases - metabolism
Protozoan Proteins - metabolism
Sequence Homology, Amino Acid
Tetrahymena - cytology
Tetrahymena - drug effects
Tetrahymena - enzymology
Tetrahymena - ultrastructure
Tubulin - metabolism
Zebrafish - embryology
Zebrafish - metabolism
Zebrafish Proteins - metabolism
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Summary:In most ciliated cell types, tubulin is modified by glycylation, a posttranslational modification of unknown function. We show that the TTLL3 proteins act as tubulin glycine ligases with chain-initiating activity. In Tetrahymena, deletion of TTLL3 shortened axonemes and increased their resistance to paclitaxel-mediated microtubule stabilization. In zebrafish, depletion of TTLL3 led to either shortening or loss of cilia in several organs, including the Kupffer's vesicle and olfactory placode. We also show that, in vivo, glutamic acid and glycine ligases oppose each other, likely by competing for shared modification sites on tubulin. We propose that tubulin glycylation regulates the assembly and dynamics of axonemal microtubules and acts either directly or indirectly by inhibiting tubulin glutamylation.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2009.04.008