@article{bbeda174fdbb48839665f3f9f81036a9,
title = "Ciliary rab28 and the BBSome negatively regulate extracellular vesicle shedding",
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.",
author = "Akella, {Jyothi S.} and Carter, {Stephen P.} and Ken Nguyen and Sofia Tsiropoulou and Moran, {Ailis L.} and Malan Silva and Fatima Rizvi and Kennedy, {Breandan N.} and Hall, {David H.} and Barr, {Maureen M.} and Blacque, {Oliver E.}",
note = "Funding Information: This work was funded by the National Institutes of Health (NIH) awards DK059418 and DK116606 to MMB and OD010943 to DHH, Science Foundation Ireland (SFI) principal investigator (11/PI/1037) and SFI-BBSRC (Biotechnology and Biological Sciences Research Council) partnership (16/BBSRC/ 3394) awards to OEB, and an Irish Research Council (IRC) Government of Ireland postgraduate award (GOIPG/2014/683) to SC, a New Jersey Commission on Spinal cord research (NJCSCR) postdoctoral fellowship (CSCR16FEL008) to JA. MS would like to thank Dr. Erik Jorgensen for funding his postdoctoral training. We thank Juan Wang for discussion and insight on ciliary EVs, Gloria Androwski and Helen Ushakov for excellent technical assistance, Barr labmates and the Rutgers C. elegans community for feedback and constructive criticism throughout this project, the Conway Institute imaging core facility for technical support, and WormBase. We thank Leslie Gunther-Cummins and Xheni Nishku at AECOM for assistance with high pressure freeze fixation. We also thank the National BioResource Project (Tokyo Women{\textquoteright}s Medical College, Tokyo, Japan) and Caenorhabditis Genetics Center (CGC) for strains. The CGC is supported by the National Institutes of Health - Office of Research Infrastructure Programs (P40 OD010440). Funding Information: This work was funded by the National Institutes of Health (NIH) awards DK059418 and DK116606 to MMB and OD010943 to DHH, Science Foundation Ireland (SFI) principal investigator (11/PI/1037) and SFI-BBSRC (Biotechnology and Biological Sciences Research Council) partnership (16/BBSRC/ 3394) awards to OEB, and an Irish Research Council (IRC) Government of Ireland postgraduate award (GOIPG/2014/683) to SC, a New Jersey Commission on Spinal cord research (NJCSCR) postdoctoral fellowship (CSCR16FEL008) to JA. MS would like to thank Dr. Erik Jorgensen for funding his postdoctoral training. We thank Juan Wang for discussion and insight on ciliary EVs, Gloria Androwski and Helen Ushakov for excellent technical assistance, Barr labmates and the Rutgers C. elegans community for feedback and constructive criticism throughout this project, the Conway Institute imaging core facility for technical support, and WormBase. We thank Leslie Gunther-Cummins and Xheni Nishku at AECOM for assistance with high pressure freeze fixation. We also thank the National BioResource Project (Tokyo Women?s Medical College, Tokyo, Japan) and Caenorhabditis Genetics Center (CGC) for strains. The CGC is supported by the National Institutes of Health-Office of Research Infrastructure Programs (P40 OD010440). Publisher Copyright: {\textcopyright} Akella et al.",
year = "2020",
month = feb,
doi = "10.7554/eLife.50580",
language = "English (US)",
volume = "9",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}