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 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.
Wloga
Dorota
D
Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
Webster
Danielle M
DM
Rogowski
Krzysztof
K
Bré
Marie-Hélène
MH
Levilliers
Nicolette
N
Jerka-Dziadosz
Maria
M
Janke
Carsten
C
Dougan
Scott T
ST
Gaertig
Jacek
J
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*
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