A Septin Diffusion Barrier at the Base of the Primary Cilium Maintains Ciliary Membrane Protein Distribution

TLDR

The primary cilium, present on nearly all mammalian cells, is essential for signal transduction such as Sonic hedgehog, yet the mechanism that retains ciliary membrane proteins remains unknown, leading to speculation of a diffusion barrier at its base. Hu et al. demonstrate that a septin‑based diffusion barrier at the ciliary base, involving SEPT2, is required for ciliogenesis, proper localization of ciliary membrane proteins, and Sonic hedgehog signaling.

Abstract

Staying in Place The primary cilium is found on nearly all mammalian cells and is a key regulatory organelle for proper signal transduction throughout development and in adults. Extracellular signal transduction, such as that promoted by Sonic hedgehog (Shh), requires the enrichment of receptors and downstream signaling components in the ciliary membrane. Intraflagellar transport is involved in selective trafficking of proteins into the cilium, but it is not known how these proteins are retained in the cilium. It has been speculated that a diffusion barrier exists at the base of the ciliary membrane. Now, Hu et al. (p. 436 , published online 17 June) demonstrate directly that a membrane diffusion barrier is indeed present at the base of the ciliary membrane. SEPT2, a member of the septin family that also forms a diffusion barrier in budding yeast and mammalian sperm membranes, localizes to the base of the ciliary membrane and is required for ciliogenesis, ciliary membrane protein localization, and cilium-dependent Shh signaling.