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Curr Biol. 2017 Apr 3;27(7):968-980. doi: 10.1016/j.cub.2017.02.039. Epub 2017 Mar 16.

Cell-Specific α-Tubulin Isotype Regulates Ciliary Microtubule Ultrastructure, Intraflagellar Transport, and Extracellular Vesicle Biology.

Author information

1
Department of Genetics and Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA; Waksman Institute for Microbiology, Rutgers University, Piscataway, NJ 08854, USA.
2
Waksman Institute for Microbiology, Rutgers University, Piscataway, NJ 08854, USA.
3
Center for C. elegans Anatomy, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
4
Department of Genetics and Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
5
Department of Genetics and Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA; Waksman Institute for Microbiology, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: barr@dls.rutgers.edu.

Abstract

Cilia are found on most non-dividing cells in the human body and, when faulty, cause a wide range of pathologies called ciliopathies. Ciliary specialization in form and function is observed throughout the animal kingdom, yet mechanisms generating ciliary diversity are poorly understood. The "tubulin code"-a combination of tubulin isotypes and tubulin post-translational modifications-can generate microtubule diversity. Using C. elegans, we show that α-tubulin isotype TBA-6 sculpts 18 A- and B-tubule singlets from nine ciliary A-B doublet microtubules in cephalic male (CEM) neurons. In CEM cilia, tba-6 regulates velocities and cargoes of intraflagellar transport (IFT) kinesin-2 motors kinesin-II and OSM-3/KIF17 without affecting kinesin-3 KLP-6 motility. In addition to their unique ultrastructure and accessory kinesin-3 motor, CEM cilia are specialized to produce extracellular vesicles. tba-6 also influences several aspects of extracellular vesicle biology, including cargo sorting, release, and bioactivity. We conclude that this cell-specific α-tubulin isotype dictates the hallmarks of CEM cilia specialization. These findings provide insight into mechanisms generating ciliary diversity and lay a foundation for further understanding the tubulin code.

KEYWORDS:

C. elegans; cilia; extracellular vesicles; glutamylation; intraflagellar transport; kinesin-3; microtubule; polycystin; post-translational modifications; tubulin

PMID:
28318980
PMCID:
PMC5688951
DOI:
10.1016/j.cub.2017.02.039
[Indexed for MEDLINE]
Free PMC Article

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