PUBLICATION

Cytoplasmic carboxypeptidase 5 regulates tubulin glutamylation and zebrafish cilia formation and function

Authors
Pathak, N., Austin-Tse, C.A., Liu, Y., Vasilyev, A., Drummond, I.A.
ID
ZDB-PUB-140513-128
Date
2014
Source
Molecular biology of the cell   25(12): 1836-44 (Journal)
Registered Authors
Drummond, Iain, Liu, Yan, Pathak, Naremdra, Vasilyev, Aleksandr
Keywords
none
MeSH Terms
  • Animals
  • Carboxypeptidases/physiology*
  • Cilia/physiology*
  • Gene Knockdown Techniques
  • Glutamic Acid/metabolism*
  • Larva/cytology
  • Larva/enzymology
  • Microtubules/metabolism
  • Pronephros/cytology
  • Pronephros/enzymology
  • Protein Processing, Post-Translational
  • Tubulin/metabolism*
  • Zebrafish
  • Zebrafish Proteins/physiology*
PubMed
24743595 Full text @ Mol. Biol. Cell
Abstract
Glutamylation is a functionally important tubulin posttranslational modification enriched on stable microtubules of neuronal axons, mitotic spindles, centrioles and cilia. In vertebrates, balanced activities of tubulin glutamyl ligase and cytoplasmic carboxypeptidase deglutamylase enzymes maintain organelle and cell type specific tubulin glutamylation patterns. Tubulin glutamylation in cilia is regulated via restricted subcellular localization or expression of tubulin glutamyl ligases (ttlls) and nonenzymatic proteins including the zebrafish TPR repeat protein Fleer/Ift70. Here we analyzed the expression patterns of ccp deglutamylase genes during zebrafish development and the effects of ccp gene knockdown on cilia formation, morphology, and tubulin glutamylation. The deglutamylases, ccp2, ccp5 and ccp6 were expressed in ciliated cells, whereas ccp1 expression was restricted to the nervous system. Only ccp5 knockdown increased cilia tubulin glutamylation, induced ciliopathy phenotypes including axis curvature, hydrocephalus, pronephric cysts and disrupted multicilia motility, suggesting that Ccp5 is the principal tubulin deglutamylase that maintains functional levels of cilia tubulin glutamylation. The ability of ccp5 knockdown to restore cilia tubulin glutamylation in fleer/ift70 mutants and rescue pronephric multicilia formation, both in fleer and ift88-deficient zebrafish, indicates that tubulin glutamylation is a key driver of ciliogenesis.
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