The tubulin deglutamylase CCPP-1 regulates the function and stability of sensory cilia in C. elegans

Robert O'Hagan, Brian P. Piasecki, Malan Silva, Prasad Phirke, Ken C.Q. Nguyen, David H. Hall, Peter Swoboda, Maureen M. Barr

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Background: Posttranslational modifications (PTMs) such as acetylation, detyrosination, and polyglutamylation have long been considered markers of stable microtubules and have recently been proposed to guide molecular motors to specific subcellular destinations. Microtubules can be deglutamylated by the cytosolic carboxypeptidase CCP1. Loss of CCP1 in mice causes cerebellar Purkinje cell degeneration. Cilia, which are conserved organelles that play important diverse roles in animal development and sensation, contain axonemes comprising microtubules that are especially prone to PTMs. Results: Here, we report that a CCP1 homolog, CCPP-1, regulates the ciliary localization of the kinesin-3 KLP-6 and the polycystin PKD-2 in male-specific sensory neurons in C. elegans. In male-specific CEM (cephalic sensilla, male) cilia, ccpp-1 also controls the velocity of the kinesin-2 OSM-3/KIF17 without affecting the transport of kinesin-II cargo. In the core ciliated nervous system of both males and hermaphrodites, loss of ccpp-1 causes progressive defects in amphid and phasmid sensory cilia, suggesting that CCPP-1 activity is required for ciliary maintenance but not ciliogenesis. Affected cilia exhibit defective B-tubules. Loss of TTLL-4, a polyglutamylating enzyme of the tubulin tyrosine ligase-like family, suppresses progressive ciliary defects in ccpp-1 mutants. Conclusions: Our studies suggest that CCPP-1 acts as a tubulin deglutamylase that regulates the localization and velocity of kinesin motors and the structural integrity of microtubules in sensory cilia of a multicellular, living animal. We propose that the neuronal degeneration caused by loss of CCP1 in mammals may represent a novel ciliopathy in which cilia are formed but not maintained, depriving the cell of cilia-based signal transduction.

Original languageEnglish
Pages (from-to)1685-1694
Number of pages10
JournalCurrent Biology
Volume21
Issue number20
DOIs
StatePublished - 25 Oct 2011

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Cilia
cilia
Tubulin
tubulin
Kinesin
kinesin
Microtubules
microtubules
Animals
TRPP Cation Channels
Carboxypeptidases
Acetylation
post-translational modification
Signal transduction
Defects
Mammals
Post Translational Protein Processing
Neurology
Structural integrity
Neurons

Cite this

O'Hagan, R., Piasecki, B. P., Silva, M., Phirke, P., Nguyen, K. C. Q., Hall, D. H., ... Barr, M. M. (2011). The tubulin deglutamylase CCPP-1 regulates the function and stability of sensory cilia in C. elegans. Current Biology, 21(20), 1685-1694. https://doi.org/10.1016/j.cub.2011.08.049
O'Hagan, Robert ; Piasecki, Brian P. ; Silva, Malan ; Phirke, Prasad ; Nguyen, Ken C.Q. ; Hall, David H. ; Swoboda, Peter ; Barr, Maureen M. / The tubulin deglutamylase CCPP-1 regulates the function and stability of sensory cilia in C. elegans. In: Current Biology. 2011 ; Vol. 21, No. 20. pp. 1685-1694.
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O'Hagan, R, Piasecki, BP, Silva, M, Phirke, P, Nguyen, KCQ, Hall, DH, Swoboda, P & Barr, MM 2011, 'The tubulin deglutamylase CCPP-1 regulates the function and stability of sensory cilia in C. elegans', Current Biology, vol. 21, no. 20, pp. 1685-1694. https://doi.org/10.1016/j.cub.2011.08.049

The tubulin deglutamylase CCPP-1 regulates the function and stability of sensory cilia in C. elegans. / O'Hagan, Robert; Piasecki, Brian P.; Silva, Malan; Phirke, Prasad; Nguyen, Ken C.Q.; Hall, David H.; Swoboda, Peter; Barr, Maureen M.

In: Current Biology, Vol. 21, No. 20, 25.10.2011, p. 1685-1694.

Research output: Contribution to journalArticle

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T1 - The tubulin deglutamylase CCPP-1 regulates the function and stability of sensory cilia in C. elegans

AU - O'Hagan, Robert

AU - Piasecki, Brian P.

AU - Silva, Malan

AU - Phirke, Prasad

AU - Nguyen, Ken C.Q.

AU - Hall, David H.

AU - Swoboda, Peter

AU - Barr, Maureen M.

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