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The zebrafish fleer gene encodes an essential regulator of cilia tubulin polyglutamylation.

Cilia and basal bodies are essential organelles for a broad spectrum of functions, including the development of left-right asymmetry, kidney function, cerebrospinal fluid transport, generation of photoreceptor outer segments, and hedgehog signaling. Zebrafish fleer (flr) mutants exhibit kidney cysts, randomized left-right asymmetry, hydrocephalus, and rod outer segment defects, suggesting a pleiotropic defect in ciliogenesis. Positional cloning flr identified a tetratricopeptide repeat protein homologous to the Caenorhabditis elegans protein DYF1 that was highly expressed in ciliated cells. flr pronephric cilia were shortened and showed a reduced beat amplitude, and olfactory cilia were absent in mutants. flr cilia exhibited ultrastructural defects in microtubule B-tubules, similar to axonemes that lack tubulin posttranslational modifications (polyglutamylation or polyglycylation). flr cilia showed a dramatic reduction in cilia polyglutamylated tubulin, indicating that flr encodes a novel modulator of tubulin polyglutamylation. We also found that the C. elegans flr homologue, dyf-1, is also required for tubulin polyglutamylation in sensory neuron cilia. Knockdown of zebrafish Ttll6, a tubulin polyglutamylase, specifically eliminated tubulin polyglutamylation and cilia formation in olfactory placodes, similar to flr mutants. These results are the first in vivo evidence that tubulin polyglutamylation is required for vertebrate cilia motility and structure, and, when compromised, results in failed ciliogenesis.

Pubmed ID: 17761526


  • Pathak N
  • Obara T
  • Mangos S
  • Liu Y
  • Drummond IA


Molecular biology of the cell

Publication Data

November 26, 2007

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK-53093
  • Agency: NIDDK NIH HHS, Id: DK-54711
  • Agency: NIDDK NIH HHS, Id: R01 DK078209
  • Agency: NIDDK NIH HHS, Id: R21 DK069604
  • Agency: NIDDK NIH HHS, Id: T32-DK007540-20

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Cilia
  • Conserved Sequence
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Humans
  • Microtubules
  • Molecular Sequence Data
  • Mutation
  • Olfactory Bulb
  • Phenotype
  • Polyglutamic Acid
  • Receptors, Cell Surface
  • Sequence Alignment
  • Tubulin
  • Zebrafish
  • Zebrafish Proteins