FIGURE 4:

Models for CIL-7– and KLP-6–mediated EV biogenesis. (A) KLP-6 and CIL-7 may be positive regulators of EV environmental release. In this model, EVs bud from the ciliary base and are shed into the cephalic lumen. From here, KLP-6 and IFT may propel EVs along the ciliary membrane surface to the cuticular opening. Myristoylated, membrane-associated CIL-7 is EV cargo that acts with an unidentified transmembrane tether. The tethered EV binds a ciliary surface protein that is transported by KLP-6 and IFT. Inset, the EV tethered to an unidentified protein such as a flagellar membrane glycoprotein. (B) CIL-7 and KLP-6 may act as dual negative regulators of EV shedding. Inset, a negative feedback loop with CIL-7 and KLP-6 acting in concert to regulate EV shedding. (C, D) In the absence of cil-7 or klp-6 as a positive regulator of EV release or negative regulator of EV shedding, the net result is an accumulation of EVs within the cephalic lumen. In both models, klp-6 acts within the EV-releasing ciliated sensory neurons, whereas cil-7 may act in the EV-releasing cell or in the EV itself. Insets of C and D depict EV shedding that is not regulated in the absence of CIL-7 and KLP-6, respectively. TZ, transition zone.