ZFIN ID: ZDB-PUB-090622-6
TTLL3 Is a tubulin glycine ligase that regulates the assembly of cilia
Wloga, D., Webster, D.M., Rogowski, K., Bré, M.H., Levilliers, N., Jerka-Dziadosz, M., Janke, C., Dougan, S.T., and Gaertig, J.
Date: 2009
Source: Developmental Cell   16(6): 867-876 (Journal)
Registered Authors: Dougan, Scott T., Webster, Danielle
Keywords: CELLBIO, DEVBIO
MeSH Terms:
  • Animals
  • Axoneme/drug effects
  • Axoneme/enzymology
  • Axoneme/ultrastructure
  • Body Patterning/drug effects
  • Cilia/drug effects
  • Cilia/enzymology*
  • Cilia/ultrastructure
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/enzymology
  • Gene Knockdown Techniques
  • Genes, Dominant
  • Glutamic Acid/metabolism
  • Glycine/metabolism*
  • Ligases/metabolism
  • 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*
PubMed: 19531357 Full text @ Dev. Cell
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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.
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