4.7 Article

Kinesin-2 motors differentially impact biogenesis of extracellular vesicle subpopulations shed from sensory cilia

期刊

ISCIENCE
卷 25, 期 11, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.isci.2022.105262

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资金

  1. NIH-ORIP [P40 OD010440, S10 OD016361]
  2. NIH-NIGMS [P20 GM103446, T32-GM133395, R01 GM135433]
  3. NSF [IIA-1301765]
  4. State of Delaware
  5. NIH-NIGMS INBRE [P20 GM103446]

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Extracellular vesicles (EVs) are lipid-bilayer enclosed particles released from almost all cells, and one specialized site for EV shedding is the primary cilium. The ion channel CLHM-1 is discovered as a ciliary EV cargo. Different populations of EVs, enriched with different protein cargoes, are shed in response to mating partner availability.
Extracellular vesicles (EVs) are bioactive lipid-bilayer enclosed particles released from nearly all cells. One specialized site for EV shedding is the primary cilium. Here, we discover the conserved ion channel CLHM-1 as a ciliary EV cargo. Imaging of EVs released from sensory neuron cilia of Caenorhabditis elegans expressing fluorescently tagged CLHM-1 and TRP polycystin-2 channel PKD-2 shows enrichment of these cargoes in distinct EV subpopulations that are differentially shed in response to mating partner availability. PKD-2 alone is present in EVs shed from the cilium distal tip, whereas CLHM-1 EVs bud from a secondary site(s), including the ciliary base. Heterotrimeric and homodimeric kinesin-2 motors have discrete impacts on PKD-2 and CLHM-1 colocalization in both cilia and EVs. Total loss of kinesin-2 activity decreases shedding of PKD-2 but not CLHM-1 EVs. Our data demonstrate that anterograde intraflagellar transport is required for selective enrichment of protein cargoes into heterogeneous EVs with different signaling potentials.

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