Model for the role of Cdc42 and the exocyst in delivery of ciliary proteins. (A) Data support a model in which the exocyst complex is localized to the primary cilium by Cdc42, which is located all along the apical surface, but is activated at the primary cilium by Tuba, a Cdc42 GEF. The exocyst is then stabilized by Sec10 binding directly to the Par complex via Par6. Once the exocyst complex is stabilized at the nascent primary cilium, it then targets and docks vesicles carrying ciliary proteins, by interacting with a small GTPase, Rab8, found on vesicles. (B) When Cdc42 (or the exocyst or the PAR complex) is lacking in a cell, the exocyst no longer localizes to primary cilia and increased cell proliferation, apoptosis, and fibrosis occur, with the result being ciliary phenotypes (hydrocephalus, small eyes, tail curvature, and edema in zebrafish; and PKD in mice). (Reproduced with permission from the Journal of American Society of Nephrology).