Primary cilia are required for the efficient functioning of any organism, and their dysfunction in humans has been implicated in numerous diseases. One of the underlying causes of ciliary defects could be the mislocalisation of ciliary signalling proteins. Adenylyl cyclase 3 (AC3) localises to the cilia of olfactory sensory neurons (OSNs) and is required for odorant detection. However, little is known about the signals that target AC3 to the cilia. In this issue (p. ), Jeffrey Martens and colleagues investigated the role of small ubiquitin-like modifier (SUMO) proteins in targeting AC3 to cilia by using both cell culture and in vivo approaches. They identified a putative conserved SUMO modification site in AC3 and demonstrated that AC3 is SUMOylated in vivo. AC3 could not localise to cilia when its SUMOylation site was mutated, or when the SUMO-cleaving peptidase SENP2 was overexpressed in the cytoplasm, indicating that SUMOylation is necessary for the targeting of AC3 to cilia in OSNs. Interestingly, SUMOylation alone was insufficient for targeting a protein to the cilia, because introducing the functional SUMO motif from the cilium-localised anoctamin 2 (ANO2) into its homologue ANO1 – which is not normally found at cilia – did not result in its ciliary localisation. Taken together, this study shows not only that SUMOylation can contribute to the targeting of certain proteins to the cilia but also that mutations in SUMO motifs might be the underlying basis of certain cilium-associated diseases.
