Ciliary diffusion barrier: The gatekeeper for the primary cilium compartment

The primary cilium is a cellular antenna that detects and transmits chemical and mechanical cues in the environment through receptors and downstream signal proteins enriched along the ciliary membrane. While it is known that ciliary membrane proteins enter the cilium by way of vesicular and intraflagellar transport, less is known about how ciliary membrane proteins are retained in, and how apical membrane proteins are excluded from the cilium. Here, we review evidence for a membrane diffusion barrier at the base of the primary cilium, and highlight the recent finding of a septin cytoskeleton diffusion barrier. We also discuss candidate ciliopathy genes that may be involved in formation of the barrier, and the role of a diffusion barrier as a common mechanism for compartmentalizing membranes and lipid domains.