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

Malan Silva, Natalia Morsci, Ken C.Q. Nguyen, Anza Rizvi, Christopher Rongo, David H. Hall, Maureen M. Barr

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)968-980
Number of pages13
JournalCurrent Biology
Volume27
Issue number7
DOIs
StatePublished - Apr 3 2017

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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