The cytosolic carboxypeptidases (CCPs) are a subfamily of metalloenzymes within the larger M14 family of carboxypeptidases
that have been implicated in the post-translational modification of tubulin. It has been suggested that at least four of the
six mammalian CCPs function as tubulin deglutamylases. However, it is not yet clear whether these enzymes play redundant or
unique roles within the cell. To address this question, genes encoding CCPs were identified in the zebrafish genome. Analysis
by quantitative polymerase chain reaction (qPCR) indicated that CCP1, CCP2, CCP5, and CCP6 mRNA were detectable between 2
hours and 8 days post fertilization, with highest levels 5-8 days post fertilization. CCP1, CCP2, and CCP5 mRNAs were predominantly
expressed in tissues such as the brain, olfactory placodes and pronephric ducts. Morpholino oligonucleotide-mediated knockdown
of CCP1 and CCP5 mRNA resulted in a common phenotype including ventral body curvature and hydrocephalus. Confocal microscopy
of morphant zebrafish revealed olfactory placodes with defective morphology as well as pronephric ducts with increased polyglutamylation.
These data suggest that CCP1 and CCP5 play important roles in developmental processes, particularly the development and functioning
of cilia. The robust and similar defects upon knockdown suggest that each CCP may have a function in microtubule modification
and ciliary function and that other CCPs are not able to compensate for the loss of one.