title: TTLL3 Is a tubulin glycine ligase that regulates the assembly of cilia.
abstract: 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.
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Dorota
authors.initials: D
authors.lastname: Wloga
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Webster
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Rogowski
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Bré
authors.forename: Nicolette
authors.initials: N
authors.lastname: Levilliers
authors.forename: Maria
authors.initials: M
authors.lastname: Jerka-Dziadosz
authors.forename: Carsten
authors.initials: C
authors.lastname: Janke
authors.forename: Scott T
authors.initials: ST
authors.lastname: Dougan
authors.forename: Jacek
authors.initials: J
authors.lastname: Gaertig
mesh_terms: D000818:Animals; D054468:Axoneme / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D019521:Body Patterning / Q000187:drug effects; D002923:Cilia / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000201:enzymology; D055785:Gene Knockdown Techniques; D005799:Genes, Dominant; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010453:Peptide Synthases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013768:Tetrahymena / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D014404:Tubulin / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D016376:Oligonucleotides, Antisense; D015800:Protozoan Proteins; D014404:Tubulin; D029961:Zebrafish Proteins; D018698:Glutamic Acid; D008025:Ligases; D010453:Peptide Synthases; C541930:Ttll3 protein, zebrafish; D005998:Glycine