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Ciliary Rab28 and the BBSome negatively regulate extracellular vesicle shedding
Jyothi S Akella1, Stephen P Carter2, Ken Nguyen3
1Department of Genetics and Human Genetics Institute of New Jersey, Rutgers University, Piscataway, United States.
Elife
|February 27, 2020
Summary
Cilia use extracellular vesicles (EVs) for communication. This study reveals Rab28 and the BBSome regulate ciliary EV production, impacting sensory organ development and potentially human ciliopathies.
Area of Science:
- Cell Biology
- Genetics
- Neuroscience
Background:
- Cilia are crucial cellular structures involved in sensory perception and signaling.
- Extracellular vesicles (EVs) act as nano-communication devices, but mechanisms of ciliary EV biogenesis are largely unknown.
- Rab28, a G-protein linked to cone-rod dystrophy, is implicated in cellular processes.
Purpose of the Study:
- To investigate the mechanisms regulating extracellular vesicle (EV) production in cilia.
- To determine the role of the G-protein Rab28 in ciliary EV biogenesis.
- To explore the connection between ciliary EV production and sensory organ development.
Main Methods:
- Utilized *Caenorhabditis elegans* as a model organism to study ciliary function.
- Investigated the localization and function of Rab28 within cilia and periciliary membranes.
- Analyzed the impact of BBSome and PDE6D proteins on Rab28 targeting and EV production.
- Examined sensory compartment morphogenesis in EV-defective mutants.
Main Results:
- Rab28 negatively regulates ciliary EV levels in a cilia-specific manner.
- Rab28 targeting to ciliary membranes depends on the BBSome and PDE6D.
- Loss of BBSome leads to excessive and ectopic EV production.
- Mutants with defective EVs exhibit sensory compartment morphogenesis abnormalities.
Conclusions:
- Rab28 and the BBSome are critical in vivo regulators of EV production at the periciliary membrane.
- Cilia-derived EVs may mediate signaling between cilia and glia, shaping sensory organ compartments.
- Defects in ciliary EV biogenesis could contribute to human ciliopathies like cone-rod dystrophy.
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