Cell-Specific α-Tubulin Isotype Regulates Ciliary Microtubule Ultrastructure, Intraflagellar Transport, and Extracellular Vesicle Biology.
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.
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.
Malan
M
Silva
Waksman Institute for Microbiology, Rutgers University, Piscataway, NJ 08854, USA.
Natalia
N
Morsci
Center for C. elegans Anatomy, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ken C Q
KCQ
Nguyen
Department of Genetics and Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
Anza
A
Rizvi
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.
Christopher
C
Rongo
Center for C. elegans Anatomy, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
David H
DH
Hall
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.
Maureen M
MM
Barr
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D055032:Electron Microscope Tomography; D008297:Male; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D020033:Protein Isoforms; D014404:Tubulin
C. elegans; cilia; extracellular vesicles; glutamylation; intraflagellar transport; kinesin-3; microtubule; polycystin; post-translational modifications; tubulin