Ciliary rab28 and the BBSome negatively regulate extracellular vesicle shedding

Jyothi S. Akella, Stephen P. Carter, Ken Nguyen, Sofia Tsiropoulou, Ailis L. Moran, Malan Silva, Fatima Rizvi, Breandan N. Kennedy, David H. Hall, Maureen M. Barr, Oliver E. Blacque

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Cilia both receive and send information, the latter in the form of extracellular vesicles (EVs). EVs are nano-communication devices that influence cell, tissue, and organism behavior. Mechanisms driving ciliary EV biogenesis are almost entirely unknown. Here, we show that the ciliary G-protein Rab28, associated with human autosomal recessive cone-rod dystrophy, negatively regulates EV levels in the sensory organs of Caenorhabditis elegans in a cilia specific manner. Sequential targeting of lipidated Rab28 to periciliary and ciliary membranes is highly dependent on the BBSome and the prenyl-binding protein phosphodiesterase 6 subunit delta (PDE6D), respectively, and BBSome loss causes excessive and ectopic EV production. We also find that EV defective mutants display abnormalities in sensory compartment morphogenesis. Together, these findings reveal that Rab28 and the BBSome are key in vivo regulators of EV production at the periciliary membrane and suggest that EVs may mediate signaling between cilia and glia to shape sensory organ compartments. Our data also suggest that defects in the biogenesis of cilia-related EVs may contribute to human ciliopathies.

Original languageEnglish (US)
Article numbere50580
JournaleLife
Volume9
DOIs
StatePublished - Feb 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Akella, J. S., Carter, S. P., Nguyen, K., Tsiropoulou, S., Moran, A. L., Silva, M., Rizvi, F., Kennedy, B. N., Hall, D. H., Barr, M. M., & Blacque, O. E. (2020). Ciliary rab28 and the BBSome negatively regulate extracellular vesicle shedding. eLife, 9, [e50580]. https://doi.org/10.7554/eLife.50580