Document Type
Article
Publication Date
Fall 11-20-2017
Journal / Book Title
Current Biology
Abstract
Ciliary microtubules (MTs) are extensively decorated with post-translational modifications (PTMs), such as glutamylation of tubulin tails. PTMs and tubulin isotype diversity act as a “Tubulin Code” that regulates cytoskeletal stability and the activity of MT-associated proteins such as kinesins. We previously showed that, in C. elegans cilia, the deglutamylase CCPP-1 affects ciliary ultrastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of kinesin-2 OSM-3/KIF17, while a cell-specific α-tubulin isotype regulates ciliary ultrastructure, intraflagellar transport, and ciliary functions of extracellular vesicle (EV)-releasing neurons. Here, we examine the role of PTMs and the Tubulin Code in the cililary specialization of EV-releasing neurons using genetics, fluorescence microscopy, kymography, electron microscopy, and sensory behavioral assays. Although the C. elegans genome encodes five tubulin tyrosine ligase-like (TTLL) glutamylases, only ttll-11 specifically regulates PKD-2 localization in EV- releasing neurons. In EV-releasing cephalic male (CEM) cilia, TTLL-11 and the deglutamylase CCPP-1 regulate remodeling of 9+0 MT doublets into 18 singlet MTs. Balanced TTLL-11 and CCPP-1 activity fine-tunes glutamylation to control velocity of kinesin-2 OSM-3/KIF17 and kinesin-3 KLP-6 without affecting the IFT kinesin-II. TTLL-11 is transported by ciliary motors. TTLL-11 and CCPP-1 are also required for the ciliary function of releasing bioactive EVs, and TTLL-11 is itself a novel EV cargo. Therefore, MT glutamylation, as part of the tubulin code, controls ciliary specialization, ciliary motor-based transport, and ciliary EV release in a living animal. We suggest that cell-specific control of MT glutamylation may be a conserved mechanism to specialize the form and function of cilia.
DOI
10.1016
Book Publisher
CellPress
Montclair State University Digital Commons Citation
O'Hagan, Robert; Silva, Malan; Nguyen, Ken CQ; Zhang, Winnie; Bellotti, Sebastian; Ramadan, Yasmin; Hall, David; and Barr, Maureen M., "Glutamylation regulates transport, specializes function, and sculpts the structure of cilia" (2017). Department of Biology Faculty Scholarship and Creative Works. 11.
https://digitalcommons.montclair.edu/biology-facpubs/11
Published Citation
O'Hagan et al, Curr Biol. 2017 November 20; 27(22): 3430–3441
Included in
Genetics Commons, Molecular and Cellular Neuroscience Commons, Other Neuroscience and Neurobiology Commons