Borg3 controls septin polymerization for primary cilia formation.

Septin GTPases form hexa- or octameric rods that polymerize into higher order structures and integrate into the cytoskeleton, playing crucial roles in cellular functions. Among these, they are involved in the formation of primary cilia-cellular signaling hubs. It is established that septins localize to cilia and contribute to their formation and function; here, we aim to gain further insights into their oligomeric composition, assembly, and regulation in the confined ciliary compartment. Using cultured cells we demonstrate, that septins enter cilia as octamers and require polymerization for ciliary enrichment. Ciliary localization of septin filaments depends on Borg3, also known as Cdc42ep5, which we identify as an essential component of primary cilia. Knockout of Borg3 as well as dysregulation of Cdc42 impairs septin dynamics and enrichment within cilia. Borg3 localization is regulated by the cycling of the Rho-GTPase Cdc42 between its inactive- and active states confined at the ciliary base.