PUBLICATION
The Zebrafish fleer Gene Encodes an Essential Regulator of Cilia Tubulin Polyglutamylation
- Authors
- Pathak, N., Obara, T., Mangos, S., Liu, Y., and Drummond, I.A.
- ID
- ZDB-PUB-070907-22
- Date
- 2007
- Source
- Molecular biology of the cell 18(11): 4353-4364 (Journal)
- Registered Authors
- Drummond, Iain, Liu, Yan, Mangos, Steve, Obara, Tomoko
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Animals, Genetically Modified
- Base Sequence
- Caenorhabditis elegans/genetics
- Caenorhabditis elegans/metabolism
- Caenorhabditis elegans Proteins/genetics
- Caenorhabditis elegans Proteins/metabolism
- Cilia/metabolism
- Conserved Sequence
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental
- Humans
- Microtubules/metabolism
- Molecular Sequence Data
- Mutation/genetics
- Olfactory Bulb/embryology
- Olfactory Bulb/metabolism
- Phenotype
- Polyglutamic Acid/metabolism*
- Receptors, Cell Surface/genetics
- Receptors, Cell Surface/metabolism
- Sequence Alignment
- Tubulin/chemistry*
- Tubulin/metabolism*
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 17761526 Full text @ Mol. Biol. Cell
Citation
Pathak, N., Obara, T., Mangos, S., Liu, Y., and Drummond, I.A. (2007) The Zebrafish fleer Gene Encodes an Essential Regulator of Cilia Tubulin Polyglutamylation. Molecular biology of the cell. 18(11):4353-4364.
Abstract
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 C. 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 post-translational 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 homolog, 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping