Presentation/Session Information

Session Information

Session Title: Cytoskeleton and Trafficking Session Type: Parallel
Session Location: Northwest Auditorium Session Time: Fri, Jun 26 8:30AM - 11:30AM

Presentation Information

Program Number: 117 Presentation Time: 9:30AM - 9:42AM

Presentation Content

Post-translational microtubule glutamylation levels control ciliary motor transport, microtubule structure, and cytoskeletal stability.Robert O'Hagan 1, Malan Silva 1, Ken Nguyen 2, Margaret Morash 1, Sebastian Bellotti 1, David Hall 2, Maureen Barr 1. 1)Dept Genetics, Rutgers, The State Univ NJ, Piscataway, NJ; 2)Center for C. elegans Anatomy, Albert Einstein College of Medicine, 1410 Pelham Parkway, Bronx NY 10461

     Post-translational modifications (PTMs) added to microtubules (MTs) may act as a “Tubulin Code” that guides the activities of kinesins, dyneins, and other MT-binding proteins. Ciliary MTs are highly decorated with PTMs, but the functions of PTMs in cilia are largely unknown. We previously showed that loss of CCPP-1, a predicted MT deglutamylase, caused defective localization of the ciliary receptor PKD-2 and the kinesin-3 motor KLP-6, and abnormally fast movement of the kinesin 2 OSM-3, in male-specific B-type neuronal cilia.  In amphid channel cilia, ccpp-1 mutants displayed a progressive Dyf phenotype and deterioration of MT structure.  Loss of a CCPP-1 homolog in mice also affects ciliated cells, causing degeneration of cerebellar Purkinje neurons, olfactory mitral cells, and retinal photoreceptors, and also causes sperm immotility.  Therefore, MT glutamylation may play a conserved role in cilia and flagella.

     Here we show that select Tubulin Tyrosine Ligase-Like (TTLL) MT glutamylases oppose the activity of CCPP-1.  Mutations in ttll-4, ttll-5, or ttll-11 suppressed the ccpp-1 progressive Dyf phenotype, but did not suppress PKD-2 ciliary localization defects.  The ttll-11 mutation suppressed ccpp-1 effects on kinesin-3 KLP-6 localization and kinesin-2 OSM-3 velocity.  

     Ciliary MT structure typically contains doublets composed of A- and B- tubules.  Ultrastructural analysis revealed loss of ciliary B-tubules in ccpp-1, while ttll-11 mutants displayed abnormally long ciliary doublet regions. MT glutamylation reduced B-tubule stability in both neuronal types, despite differences in structural details.  We hypothesize that glutamylation targets MTs for degradation by MT-severing enzymes.  To elucidate the pathways by which glutamylation controls ciliary MT stability, we performed a screen for suppressors of the ccpp-1 Dyf phenotype.  Our screen should identify molecules upstream and downstream of MT glutamylation.

     Our data suggest that, in cilia, MT glutamylation is part of a Tubulin Code that regulates ciliary transport of molecular motors and sensory receptors and controls axonemal structure.




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