Borg3 controls septin recruitment for primary cilia formation

Septin GTPases form linear hexa- or octameric rods that polymerize into higher order structures. They are incorporated into the cytoskeleton and involved in vital cellular functions. Among these, they play a role in the formation of primary cilia. Primary cilia are evolutionary conserved cellular signaling hubs. While it is accepted that septins localize to primary cilia and are involved in their formation and function, the regulation of septin assembly in the confined ciliary compartment remains elusive. Here we show, that Borg3, also known as Cdc42 effector protein 5 (Cdc42EP5), is an essential component of primary cilia. Specific Borg3 localization is facilitated by switching the Rho-GTPase Cdc42 between an inactive- and active state at the base of the primary cilium. The active form of Cdc42 has a defined localization restricted to the base of the primary cilium. Knockout of Borg3 as well as dysregulation of Cdc42 reduces septin dynamics at cilia and consequently, the formation of cilia.

The study demonstrates that Borg3 is a novel and essential regulator of ciliogenesis through the spatiotemporal control of septin dynamics downstream of Cdc42.