Figure 8. Hypothetical model of how BBS3 enters cilia to promote ciliary exit of PLD via the BBSome in C. reinhardtii.

IFT22 and BBS3 both in a GTP-bound configuration recruit the BBSome to the basal body, where the BBSome separates from BBS3 and loads onto the anterograde IFT trains by coupling with IFT-B1 and enters cilia via IFT (Xue et al., 2020). GTP-bound IFT22 is released from BBS3 and binds IFT-B1 through a direct interaction between IFT22 and the IFT74/81 sub-complex for ciliary entry (Bhogaraju et al., 2013; Lucker et al., 2010; Taschner et al., 2014). GTP-bound BBS3 then associates with the cell membrane to diffuse into cilia. PLD enters cilia by diffusion on membrane (Liu and Lechtreck, 2018). At the ciliary tip, the BBSome is released from anterograde IFT trains through BBSome/IFT train remodeling (Xue et al., 2020). GTP-bound BBS3 binds and recruits the BBSome to the ciliary membrane for interacting with PLD (Liu and Lechtreck, 2018). PLD-laden BBSomes then load onto retrograde IFT trains by coupling with IFT-B1 for ciliary exit (Xue et al., 2020). The kinesin-II anterograde motor and the cytoplasmic dynein-1b retrograde motor are also shown (Cole et al., 1998; Pazour et al., 1998). After turnaround at the ciliary tip, kinesin-II diffuses back to the ciliary base (Chien et al., 2017; Hendel et al., 2018).